From his home in Marseilles, millionaire Alain Charnier runs the largest heroin-smuggling syndicate in the world, employing ruthless Pierre Nicoli to assassinate his adversaries. While they refine their plan to smuggle $32 million worth of heroin into the United States by hiding it in the car of their new accomplice, French television personality Henri Devereaux, in New York City two police detectives continue their dogged pursuit of drug dealers. Jimmy "Popeye" Doyle and his partner, Buddy "Cloudy" Russo, use intimidation and psychological tactics to taunt and trap their targets, sometimes skirting the boundaries of ethical behavior. One night after a typically grueling day of chasing down suspects, Popeye convinces Cloudy to go to the local club with him for a drink. There, Popeye, who thinks of little else besides his job, grows suspicious of the patrons at one table who are celebrating boisterously. "Just for fun," he and Cloudy tail the main carouser, Sal Boca, all night until he returns to the diner he runs with his wife Angie. Days later, they are still watching Sal, who has a record of petty crimes, as does his brother Lou. Cloudy, posing as a patron, is able to observe the steady traffic of local businessmen who hold clandestine meetings in the back room with Sal. One day, the detectives tail Sal to the apartment building of drug financier Joel Weinstock, and exult that they have finally connected him to a known criminal. To obtain insider information, Popeye storms into a gritty bar frequented by drug users and small-time dealers. Shoving the customers against the wall and humiliating them, Popeye picks their pockets for drugs and makes a few arrests. His real aim, however, is to meet in private with one of the dealers, Hector, who is his secret informant, without arousing the others' suspicions. To that end, Popeye roughs up Hector and pulls him into the back room, and after Hector reveals that a shipment of heroin is due into the New York harbor soon, Popeye punches him to make their "confrontation" appear real. The detectives bring their case to their captain, Walter Simonson, who derides the circumstantial evidence and berates them for failing to break a big case. Together, the partners manage to convince Simonson to allow them two wiretaps, one on Sal's diner and the other on his house. Days later, at the same time as Charnier and Nicoli, newly arrived in New York, watch Devereaux's car being transported onto the wharf, federal agents Bill Mulderig and Klein are brought onto the case. Mulderig dislikes Popeye because, on a previous case, the detective's rough tactics resulted in the death of a policeman. Cloudy, who attempts to defend his partner, later visits Popeye's apartment and finds him handcuffed to the bed by a young sexual partner. Over the next few days, Popeye and Cloudy follow Sal's conversations on the wiretap, and one day they rejoice to hear a Frenchman call and make an appointment to meet. In the car on the way to the planned rendezvous, as Mulderig razzes Popeye from the backseat, they are caught in a traffic jam that endangers their ability to follow Sal. Popeye races out onto the street to catch sight of Sal's car, and soon the police are back on his trail as he enters the Roosevelt hotel. There, they spot Sal with Charnier and Nicoli, then follow them to a restaurant, standing on the freezing street while the Frenchmen enjoy a leisurely gourmet meal. Charnier leads Popeye to his hotel, where the detective is able to learn the Frenchmen's names from the clerk. Soon after, Sal brings the heroin to Weinstock, whose drug expert tests it and reports that it is high-grade, valuable dope. However, Weinstock, knowing the police are after Sal, insists on taking more time before agreeing to Charnier's price. Meanwhile, Charnier slips away from the federal agents posted around his hotel and walks along the street, where Popeye is shocked to spot him. Popeye follows him into the subway, but as he attempts to trail him, the wily Charnier manages to evade him, waving as his subway car speeds away from the detective. Klein follows Sal to Washington, D.C, where Sal meets with Charnier to ask for a few more days. Charnier insists on having the money by the end of the week, then tells Nicoli to kill Popeye, as he poses the biggest threat to their deal. At the same time, Simonson informs Popeye that, with no movement on the case, he must close it down. The furious Popeye, unable to convince Simonson to give him more time, fights with Mulderig. Soon after, Popeye is walking near his apartment when Nicoli, hiding on a rooftop, shoots at him. Popeye tries to secure the area, then crawls along the building's side until he can climb to the roof. There, he is able to spot Nicoli and races to follow him into an elevated subway platform. As Nicoli steps onto a car, a transit guard hears Popeye yell a warning, causing him to follow Nicoli suspiciously as he travels from car to car. On the ground, Popeye commandeers a passerby's car and speeds to the next subway station, hoping to reach it before the train. On the el, Nicoli shoots and kills the policeman, then holds the driver at gunpoint and commands him not to stop at the station. Popeye arrives at the stop and runs to platform, but when the train does not slow down, he jumps back into his car and careens wildly through the city streets, narrowly avoiding other cars and pedestrians, to reach the next station. Nicoli has confronted the conductor and passengers with his gun drawn, and now shoots the conductor as the driver suffers a heart attack. The train, rushing out of control, slams directly into a parked train. Below, Popeye sees the wreck and, stopping his car, walks disoriented to the bottom of the el stairs. Nicoli climbs through a door to the outside of the cars, crawling between them in order to escape the wrecked train, but as he reaches the top of the station stairs, Popeye gets him in his gun sights. Nicoli, now unarmed, turns to run, but Popeye shoots him in the back, killing him. Soon after, Popeye and Cloudy are following Sal when as he picks up Devereaux's car. They pursue the car to the street where Sal parks it, and watch for days as it sits untouched. When some men approach the car, Popeye arrests them, and although they are soon revealed to be petty car thieves, he orders the car torn apart. The police mechanic rips apart the entire car but finds nothing. Popeye, insisting the heroin is in the car, urges him to try again, and this time, they uncover 120 pounds of dope in the front grille. Hours later, they have replaced the heroin and rebuilt the car, which they return to Devereaux in order to trail him. Devereaux, spooked by the police interest, informs Charnier that he no longer wants to be involved. Charnier and Nicoli then drive the car to meet with Weinstock and his men at an abandoned warehouse, where they swap the drugs for cash. Sal, exulting in his new wealth, drives off with Charnier, only to find the bridge closed off by Popeye and his men. They return to the warehouse, where all of the criminals scatter, followed by the police. Popeye, obsessed with catching Charnier, stalks through the dilapidated building. When he hears footsteps, he turns and shoots, accidentally killing Mulderig. Although Cloudy is horrified, Popeye single-mindedly continues his pursuit, wandering off into the shadows, where a lone shot rings out.