After more surveillance, the two narcotics detectives soon learn that the Boca's small business couldn't support their lavish lifestyle (their business is only a "front"), and that they both have a suspicious history of criminal activities:

Our friend's name is Boca, Salvatore Boca. B-O-C-A. They call him Sal. He's a sweetheart. He was picked up on suspicion of armed robbery. Now get this. Three years ago, he tries to hold up Tiffany's on Fifth Avenue in broad daylight. He could have got two and a half to five. But Tiffany's wouldn't prosecute. Also, downtown, they're pretty sure he pulled off a contract on a guy named DeMarco... (Angie) - She's a fast filly. She drew a suspended for shop-lifting a year ago. She's only a kid - nineteen according to the marriage license...hmmm, nineteen going on fifty...He's had the store a year and a half. Takes in a fast seven grand a year...So what's he doin' with two cars and hundred dollar tabs at the Shea?...The LTD's in his wife's name. The Comet belongs to his brother, Lou [Benny Marino]. He's a trainee at the garbageman's school on Wards Island. He did time a couple of years ago. Assault and robbery.

Sal eventually leads them to the Manhattan apartment of his Jewish drug kingpin Joel Weinstock (Harold Gary), a wealthy financial backer of illicit drug importation into the country.

In a shakedown in a sleazy bar, Popeye announces: "Popeye's here," forces the patrons into a lineup against the wall, watches pill containers drop to the floor, and grills another suspect: "Do you pick your feet?" As he cleans the bottom-side of the bar counter of drugs, he quizzically asks: "What is this? A f--kin' hospital here? Huh?" From one of his informants (Al Fann), Doyle learns the reason why everyone's clean and there are no hard drugs on the streets: "Ain't nothin' around...There's been some talk...- a shipment, comin' in this week, the week after. Everybody's gonna get well."

Because his hunches have "backfired" before, Popeye is denied permission by his boss Lieutenant Walter Simonson (Eddie Egan) to work on his current hunches about Boca and Weinstock: "Big score, my ass. At best, he's sellin' nickel and dime bags." But they plead with Simonson to get a court order to allow them two wiretaps ("one on the store, one on the house") and to continue their pursuit in a special assignment:

Buddy: We got the information there's no s--t on the street, right? It's like a god-damn desert full of junkies out there. Everybody waiting to get well.
Doyle: This could be it!...

In Marseilles, the crafty Charnier stashed heroin into the specially-designed Lincoln Continental Mark III car of French TV celebrity/star Henri Devereaux (Frederic de Pasquale) who unwittingly escorts the shipment to New York. [Coincidentally, a month before the film opened, a drug stash of 230 lbs. of heroin was intercepted in a car on a boat from France.]

Two other federal agents, Mulderig (Bill Hickman) and Klein (Sonny Grosso) are also assigned to follow up on the case and join the pursuit, but Mulderig is an old nemesis of Popeye's. Russo and Doyle, the two nattily-dressed, overworked, uneducated New York street cops attempt to bring to justice the French drug smuggling ring. As the two supercops trail their "French connection" suspects through Manhattan, they must eat cold pizza out in the cold as the two smugglers dine in the warmth of a fancy restaurant. In a richly-appointed suite in the Westbury Hotel while testing the quality of the heroin in front of Boca and Weinstock, the chemist (Pat McDermott) watches the rising thermometer:

Blast off - one eight O.
Two hundred - Good Housekeeping Seal of Approval.
Two ten - US Government certified.
Two twenty - lunar trajectory, junk of the month club, sirloin steak.
Two thirty - Grade A poison.
Absolute dynamite. Eighty-nine percent pure junk. Best I've ever seen. If the rest is like this, you'll be dealing on this load for two years.

The two Americans discuss a deal with the French drug syndicate for a half-million dollar buy of the shipment of 60 kilos of heroin from the French foreign market - a deal worth $32 million on the street. The experienced Weinstock exercises caution toward the fidgety, impulsive Boca, the Brooklyn contact: "This is your first major league game, Sal. One thing I learned. Move calmly, move cautiously. You'll never be sorry."

When Charnier arrives in New York, he immediately senses that he is being trailed by Doyle. Popeye attempts to discreetly follow Charnier through the underground subway system. Doyle phones into his FBI colleague Mulderig: "This is Doyle. I'm sittin' on Frog One." The clever, suave Frenchman with a silver-handled umbrella outwits Doyle, smugly waving goodbye through the departing subway train window. Having been identified, Popeye becomes a prime target for elimination.

Charnier's hired, murderous sniper Pierre Nicoli ("Frog Two") muffs his attempt to kill Doyle, and is pursued in an exciting, pulsating and brilliant car-train chase sequence through Bensonhurst, Brooklyn. In one of the best pursuits ever put on film [rivaling the producer's previous car-chase scene in the film Bullitt - and the reason the film was awarded an Oscar for Best Editing], Doyle flags down and hijacks a motorist's Pontiac Le Mans (for a "police emergency") and pursues the drug dealer on board the out-of-control, run-away elevated commuter subway train (where he has terrorized passengers, killed the train's cop and conductor, and caused the motorman to have a heart-attack). He weaves in and out of traffic and track supports at top speed through the streets of New York below, barely missing a mother and baby carriage at one point, while driving with one eye on the street and one eye on the train above. At the end of the chase after a climactic train crash [photographed with the train moving away from the camera - and then reversed], Nicoli escapes from the wreckage, believing that he is free of Doyle. But Doyle guns him down at the top of the train depot stairs - the image became the famous promotional still used to advertise the film on posters.

After a search of Devereaux's car turns up nothing, Buddy deduces that the car is 120 lbs overweight - he insists that the car still conceals the heroin shipment. The bags of white powder are found hidden in the rocker panels. When the car is returned intact to Devereaux, the heroin deal is allowed to continue.

In the finale as the police close in on the criminals on Wards Island following the heroin deal, there is a massive ambush and shoot-out. The film concludes with Boca's killing and Weinstock's arrest. As Doyle and Buddy pursue their prey through a subterranean warehouse on Wards Island, Mulderig is accidentally killed by Doyle. The perturbed and frustrated cop is relentlessly obsessive in his search for the elusive Charnier (who evidently slipped away and was never caught):

The son of a bitch is here. I saw him. I'm gonna get him.

The film deliberately concludes on a mysterious note - what actually happens is ambiguous and open to varying interpretations. Doyle runs off through the warehouse to further pursue his prey. A single shot is heard - off-screen - before the film abruptly ends with a black screen. [Note: The film literally ends with a 'bang.']

Subtitles, presented about a still photo of each criminal, explain the failed denouement:

JOEL WEINSTOCK was indicted by a Grand Jury. Case dismissed for "lack of proper evidence."
ANGIE BOCA, guilty of a misdemeanor. Sentence suspended.
LOU BOCA, guilty of conspiracy and possession of narcotics. Sentence reduced.
HENRI DEVEREAUX, guilty of conspiracy. Served four years in a Federal Penitentiary.
ALAIN CHARNIER was never caught. He is believed to be living in France.
Detectives DOYLE and RUSSO were transferred out of the Narcotics Bureau and reassigned.