The effects of p.o. methadone or sublingual buprenorphine maintenance on i.v. cocaine self-administration and the response to experimenter-administered cocaine were evaluated in 12 methadone-maintained individuals. Participants lived in a clinical research center during the 4- to 5-week protocol. After stabilization on 80 mg/day methadone, half the participants were first tested during buprenorphine maintenance (8 mg/day with p.o. placebo) and half were first tested during methadone maintenance (60 mg/day with sublingual placebo). After testing on the alternate medication, all participants were returned to their entry level of methadone. Testing consisted of three daily sessions of fixed cocaine dosing (four injections; 0, 16 and 48 mg/70 kg) and three daily sessions of cocaine self-administration with a choice procedure (16, 32 and 48 mg/70 kg vs. $5). The transition from methadone to buprenorphine engendered moderate withdrawal symptoms (score of 12 on the subjective opiate withdrawal scale), which returned to base-line levels (score of 4 on the subjective opiate withdrawal scale) before testing during buprenorphine maintenance. Buprenorphine maintenance significantly reduced "I want cocaine" scores by 15% during fixed-dosing sessions. Subjective effects of fixed cocaine doses, including increased ratings of "high," "stimulated" and "good drug effect," were not affected by the maintenance medication. Heart rate was consistently 9 beats/min less, regardless of cocaine dose, during methadone maintenance. In comparison with methadone, buprenorphine maintenance decreased cocaine self-administration when 16- or 32-mg doses were available, but not when 48 mg was available. Thus, buprenorphine may have greater efficacy than methadone for controlling cocaine abuse among individuals dependent on opioids.