Late fall 1989 : even with Christmas and New Year’s Eve coming, New Yorkers remain aggressive, loud and obnoxious people. Back from the grocery store, Dana Barrett, now living on East 77th Street, doesn’t realize her carriage just rolled inside a puddle of pink slime, oozing from a crack in the pavement. But soon, the carriage starts to supernaturally roll away, accelerating towards the VERY busy First Avenue, stopping in the middle of the crossroads, a few inches away from a speeding bus… Inside the carriage, Oscar, Dana’s 8-month old baby, is okay.
Five years after the Gozer conjuration, glory hours are long gone for the Ghostbusters : unpaid by the City, sued by many insurance companies for the destruction caused by their intervention atop « Spook Central », forbidden to work as paranormal eliminators, Ray Stantz and Winston Zeddemore are driven to act as « party clowns/scientists » for upper-class children’s birthday parties, where kids, reflecting their parents’ opinions, call them liars and losers.
Dana goes for help to Egon Spengler, who works back at the university, studying affects of human emotions – mainly negative feelings – on the physical environment, a theory Ray and he had while they were Ghostbusters. He agrees to help, enlisting Ray but promising Dana they won’t tell Peter Venkman – since they broke up in quite bad terms a few years ago.
For his part, Venkman is now the host of a TV-show, « World of the Psychic », derided and despised by every respected psychic, although one of his guests, medium Milton Anglund, seriously predicts a worrisome fact : the end of the world will happen on New Year’s Eve, that very year. Backstage, as Venkman tries to greet the Mayor of New York, he is rebuked by Jack Hardemeyer, an arrogant Peck-like bureaucrat who tells him that the Mayor, running for governor, won’t be associated with frauds.
At the Manhattan Museum of Art, Dana works at the restoration of ancient paintings – a job she took only for a while, intending to go back to orchestra next year. Her boss, impish Eastern-Europe-born Dr. Janosz Poha, harbors an evident crush on her, but to no avail. None of them notice that the last acquisition of the Museum, a huge portrait of 16th-century Romanian tyrant Vigo the Carpathian, sometimes moves by itself…
At Ray’s Occult bookstore, Egon and Ray read about cases of psychokinesis. Venkman, visiting, asks them the reason of such studies ; when they try to avoid the subject, he starts tugging at Ray’s ears until he confesses they’re helping his ex, then accompanies them to her place.
While Ray and Egon examine baby Oscar, Peter and Dana talks about the baby’s father – a musician who left them to play in London -, their past relationship, which she ended when Venkman started to consider her like « the old ball and chain » instead of asking her to marry him, a proposition she would have agreed to. Venkman bonds and plays with the baby, seemingly regretting he wasn’t his dad (and, being Venkman, mocking the kid’s father). Establishing that there’s no paranormal activity at Dana’s, nor around the baby, the Ghostbusters inspect the First Avenue crossroads ; there, the readings are over the top, indicating something do happen underneath the street.
That very night, dressed as road workers, the trio drill a hole in the roadway, uncovering a deep airshaft in which Ray is send to investigate. At the bottom of the excavation, dangling at the end of a rope about one-hundred feet under the avenue, he finds an abandoned, antique subway station where gallons and gallons of greyish pink slime flow like a river. While on the surface, Egon and Venkman are controlled by an unconvinced traffic cop and a Con Ed supervisor, Ray samples some slime, provoking a surge of activity within the slime, which creates arm-like appendages trying to grab Ray’s legs. Screaming for help, he’s hoisted back a bit too fast ; in his panic, he knocks over a pipe which falls and severs a main electric line, occasioning a total blackout on Manhattan.
Earlier that night, while working late and alone on Vigo’s painting, Janosz is suddenly shocked by lightning bolts coming for Vigo’s eyes. Then, he witnesses the painting transforming into the tyrant’s giant, floating undead talking head, who commands him to bring him a child to possess. Hesitating, Janosz is brainwashed with more lightning, becoming a faithful minion for Vigo, then going during the blackout for a impromptu visit at Dana’s, with some ghostly new powers such as headlights eyes.
A few days later, the Ghostbusters (minus Winston) appear in court, presided by « hanging judge » Wexler, where their unconvincing lawyer, Louis Tully, former lovelorn neighbor of Dana, have to contend with an efficient district attorney - herself in friendly terms with Hardemeyer. Even if the public seem still keen to acclaim the defendants, the judge openly loathes them, and his frequent angry outbursts cause the slime sample, kept as an exhibit, to seethe. After sentencing Peter, Ray and Egon to eighteen months of jail, his hate-fuelled speech against con men and charlatans causes the slime to explode, liberating two ghosts : the Scoleri brothers - murderers sentenced to die on the electric chair by Wexler - who start to destroy the courtroom and scare the people away. Terrified, Judge Wexler finally decides to recant his decision, and acquit the Ghostbusters, who track and capture the Scoleris, finally and legally going back to business.
Between missions, at the Headquarters, Egon and Ray do experiments on the slime sample, confirming their theories. The matter, « mood slime », is emotionally charged : insults and sarcasm make it boil until energetic enough to blow up, freeing ghosts ; a treatment of happy thoughts and feel-good music – such as Jackie Wilson’s tunes – turn it into a positive plasma, which they use to make a toaster dance.
At the museum, visiting Dana, Peter mocks Vigo’s painting, to Janosz’s consternation, before Dana confides in Peter she feels observed by the painting and believes it smiles at her sometimes. The following night, as she is about to give Oscar a bath, slime flow from the faucet, turning the bathtub into a monster which tries to grab the baby. Frantic, she leaves home and runs at Venkman’s for shelter. Checking on their computer, Egon and Ray learn disturbing facts about Vigo - a crazy blood-thirsty wizard and warlord, who was massacred at 105 by his long-suffering subjects but promised to resurrect – and both conclude that the presence of the painting and the increasing number of ghosts in New York are evidently related.
The following morning, on December 30th, the team go to the museum, where Venkman takes pictures of Vigo, and Stantz seems unnaturally entranced by the painting. Back to his apartment, Venkman organizes a romantic dinner date at the restaurant with Dana, asking Janine, his secretary, to babysit Oscar, which she agrees to (accompanied by Louis for the night). Meanwhile, at the headquarters, Ray and Egon examine the pictures Venkman took : they discover that the river of slime glimpsed by Ray appears at the bottom of some images, before the pictures suddenly catch fire, almost burning the duo alive, if not for Winston's intervention.
That evening, Winston, Egon and Ray go to abandoned subway tracks, looking for an access to the slime river, being utterly scared by booming voices, severed heads and a spectral train as they get closer. While trying to measure the depth of the river, Winston is pulled over into the flowing goo, caught away by the current, so his friends have to dive to save him. Emerging from the sewers, covered with untreated mood slime which compels them to fight against each other for a while, they finally discover the place where the current brought them : the forecourt of the Manhattan Museum of Art. Still dripping - and in their underwear -, the trio run to the restaurant where Dana and Peter have dinner to warn them, but they are all arrested and brought to the Mayor’s, whom they fail to convince about the seriousness of the situation. When the Ghostbusters mention they should inform the press, Hardemeyer has them committed in a psych ward on his own initiative.
Meanwhile, after he asks Vigo for - and gets - the permission to have Dana as his wife, Janosz is sent - as a flying nanny ghost - to kidnap Oscar, bringing him back to the Museum. Dana, who recognized him during the rapt, follows right after them, but as soon as she enters, a thick layer of slime starts to cover the Museum, trapping her inside, helpless, as Oscar lays on an altar in front of the painting, ready to be sacrificed the next night as Vigo’s human vessel.
The river of slime overflows and reaches the surface, turning Manhattan into pandemonium that night and the following day. The Mayor orders to call the Ghostbusters, then fires Hardemeyer upon learning his assistant sent them to the asylum. Freed at last, the team learns nothing can cut through the slime shell, not even their packs, before getting a common idea : to weaken mood slime, a lot of positive energy is required, and a well-loved symbol could raise it more than anything else. Cut on Liberty Island, where they drench the inside of Lady Liberty with positive mood slime, then turn on « Higher and higher » by Howard Huntsberry on loudspeakers, animating the statue which walks towards the museum under the joyous acclaim of all New Yorkers !
At midnight, just as Vigo starts to possess Oscar’s body, Lady Liberty strikes the Museum's roof with her torch, allowing the Ghostbusters to climb down inside and hose Janosz with positive mood slime, knocking him out. But even if the ritual was interrupted, Vigo is now « alive », out of the painting and immensely powerful, easily incapacitating the Ghostbusters and Dana before seizing Oscar one more time. Fortunately, the voices of thousands of New Yorkers assembled around the Museum, singing « Auld Lang Syne »in unison, are gradually weakening the slime river, depriving Vigo from his strength and sending him back to the painting, where he morphs into a demon-like creature… who nevertheless hypnotizes Ray and briefly possess him. After being doused over and over with positive mood slime and shot at with proton guns, Vigo finally disappears into the painting, then explodes, destroying at the same time the thick slime shell, under the bewildered eyes of Louis who, wearing Egon’s jumpsuit and an extra proton pack, was outside trying to vaporize the shell by himself – and is now hailed as a hero by people around him.
Dana and Peter kiss, before the team discovers that the painting doesn’t show Vigo’s towering figure anymore, but what was on the canvas beneath : a gorgeous early Renaissance representation of a baby, protected by four angels who look a lot like four paranormal exterminators from NYC…
