The effects of buprenorphine on behavior reinforced by smoked cocaine base and orally delivered phencyclidine (PCP), ethanol and saccharin were compared. There were six groups of four to five rhesus monkeys. Group 1 contained four monkeys that had been trained to smoke cocaine base under progressive ratio (PR) or fixed ratio (FR) schedules. Up to eight smoke deliveries (2 mg/kg) were available during daily 3-hr sessions. Each delivery was separated by a 15-min timeout. The remaining groups received concurrent access to different combinations of orally delivered liquids as follows: group 2, PCP (0.25 mg/ml) and water; group 3, saccharin (0.03% w/v) and water; group 4, PCP and saccharin; group 5, ethanol (8% w/v) and water; and group 6, ethanol and PCP. Saline or buprenorphine (0.003, 0.012, 0.05, 0.2 and 0.8 mg/kg) injections were given i.m. 30 min before each session for 5 consecutive days. Buprenorphine produced a dose-dependent reduction in behavior maintained by PCP, ethanol or saccharin in all of the six groups. In group 1, the suppressant effects of buprenorphine on cocaine base smoking were greater in the two monkeys that responded under FR 5 schedules than in the two that responded under PR schedules. When PCP and saccharin were concurrently available (group 4), buprenorphine had a greater suppressant effect on PCP than when water was concurrently present (group 2). Buprenorphine produced nearly a complete suppression in saccharin-maintained responding at doses of 0.012 mg/kg and higher in groups 3 and 4. Buprenorphine reduced ethanol deliveries to about 50% at doses of 0.012 mg/kg and higher in group 5. When PCP and ethanol were concurrently available (group 6), buprenorphine had an effect on PCP and ethanol that was similar to that found when the drugs were available concurrently with water. These results suggest that buprenorphine suppresses behavior maintained by several drug and nondrug substances, and it further suppresses PCP-maintained behavior that is already reduced by a nondrug alternative reinforcer.