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Marcus Burnett (Martin Lawrence) and Mike Lowrey (Will Smith) are best friends and detectives in the narcotics division of the Miami-Dade Police Department. One night, $100 million of seized heroin is stolen from a secure police vault. This is a major blow to Burnett and Lowrey, because it was the biggest drug bust of their careers. Internal Affairs thinks that it was an inside job and warns Miami PD that if they do not recover the drugs in five days, the narcotics division will be shut down.
Lowrey asks one of his informants and ex-girlfriend Maxine "Max" Logan to look for people, who are newly rich and therefore suspects. She gets herself and her best friend Julie Mott (Téa Leoni) hired as escorts by Eddie Domínguez, a former cop and part of the coup. His boss, French drug kingpin Fouchet (Tchéky Karyo), does not want the coup to be endangered by outsiders and therefore shoots Max and Dominguez. After witnessing the murder, Julie manages to escape over the roof.
Although she has not met Mike, because of Max's relationship with him Julie will only trust and deal with Lowrey. However, he is away when she contacts the police about the murders, threatening to run if she does not speak to Mike. Captain Conrad Howard (Joe Pantoliano) forces Burnett to impersonate Lowrey to get Julie to cooperate. In order to continue the deception, Burnett and Lowrey switch lives. Burnett tells his family he is going to Cleveland for a case, leaving Mike to stay with them.
Burnett then moves into Lowrey's apartment with Julie and her dogs. In Julie's presence, Burnett poses as Lowrey while Mike poses as Burnett.
The investigation proceeds with Lowrey and Burnett calling in on their old informants, including Jojo (Michael Imperioli), a former chemist and drug convict. Later, Julie identifies one of Max's killers, while looking through mug shots.
The two cops then head off to Club Hell, one of his known hangouts. Unbeknownst to them, Julie has followed, eager to dish out revenge on Max's killers. Though the criminals spot them first, after a brief fight and car chase, all three manage to escape. The incident is caught on camera by a news helicopter. The subsequent report is later seen by Burnett's family.
At Club Hell they discovered barrels of Ether, which is used to refine heroin, so Lowrey and Burnett decide to visit Jojo again. After an aggressive and convincing good cop-bad cop act from Lowrey and Burnett, Jojo tells them the location of the chemist who is cutting the stolen drugs. After staking out his house, they follow him to where Fouchet is hiding the drugs.
They return to Mike's apartment with Julie, where they are confronted by Marcus' wife who blows their cover, causing Julie to try to run. Fouchet and his gang arrive at Lowrey's apartment and kidnap Julie. Because of this, Internal Affairs reassigns all members of the narcotics division, effectively shutting them down, but Captain Howard delays the order to give Lowrey and Burnett a chance to get Julie and the drugs back.
Burnett, Lowrey and two other members of the Miami P.D. organize a plan to stop the criminals from killing Julie and selling the drugs. A final shoot-out erupts between the group of cops and the drug dealers at an air field. Burnett is shot in the leg after saving Julie from Fouchet. Fouchet also shoots Lowrey while escaping the building, which is now on fire, but he is rescued by Burnett and Julie who left to get Lowrey's car.
The cops and Julie chase Fouchet's Shelby Cobra AC 427 in Mike's Porsche 911 Turbo. Burnett bumps Fouchet into a concrete barrier but he manages to escape the wreckage. Attempting to run, Fouchet is shot in the leg by Lowrey. Fouchet, knowing he is beaten, tries to goad Lowrey into killing him, which he almost does as revenge for Max's murder, until Burnett prevents it.
While on the ground Fouchet then pulls out a concealed weapon and aims at Burnett, but seeing the reflection on his partner's forehead, Lowrey spins and shoots Fouchet numerous times, killing him.
Later, after Marcus and Mike profess their mutual platonic love for one another and their relief in surviving the gun fight, Marcus handcuffs Julie and Mike's hands together and hobbles away hoping for some much needed "quality time" with his wife.
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