Heroin overdose deaths have increased alarmingly in Chicago over the past decade. Naloxone, an opioid antagonist with no abuse potential, has been used to reverse opiate overdose in emergency medical settings for decades. We describe here a program to educate opiate users in the prevention of opiate overdose and its reversal with intramuscular naloxone. Participant education and naloxone prescription are accomplished within a large comprehensive harm reduction program network. Since institution of the program in January 2001, more than 3,500 10 ml (0.4 mg/ml) vials of naloxone have been prescribed and 319 reports of peer reversals received. The Medical Examiner of Cook County reported a steady increase in heroin overdose deaths since 1991, with a four-fold increase between 1996 and 2000. This trend reversed in 2001, with a 20% decrease in 2001 and 10% decreases in 2002 and 2003.