Serpico must protect John Maloney, a presidential candidate for the truck drivers' union, from an assassination ordered by current leader Jack Powell. Maloney's daughter Rita falls for Serpico. Vern Ross, Maloney's right-hand man, has a crush on Rita and secretly works for Powell.

Vince Cipolla, a 20-year veteran on the police force, is dying of leukemia and wants to leave money for his wife. He gives confidential information on the locations of gambling and prostitution houses to two criminals who share their ill-gotten gains with Cipolla. Serpico follows the clues to Cipolla, who once instructed him, and tries to help.