The effects of i.v. cocaine were examined in individuals maintained on methadone. Sixteen adult methadone-maintained i.v. cocaine users, residing on a clinical research unit, participated in eight laboratory sessions under each of two conditions: cocaine 1 hr after daily methadone and cocaine 22 hr after daily methadone. The conditions were separated by an outpatient period of 3 to 5 weeks. During the first five sessions, the cardiovascular and subjective effects of single i.v. cocaine doses (0, 8, 16, 32 or 48 mg/70 kg) were determined. During the last three sessions, the effects of i.v. cocaine (0, 8 or 32 mg/70 kg) administered 4 times per session at 14-min intervals were determined. Single and repeated doses of cocaine produced dose-dependent increases in cardiovascular effects (e.g., diastolic pressure and heart rate), subjective effects (e.g., ratings of "High," or "Stimulated") and ratings of cocaine dose (e.g., "Quality," or "Liking"), regardless of methadone dose or the timing of cocaine administration. Increases in blood pressure after single cocaine doses were greater when cocaine was given 1 hr after methadone. Subjects maintained on higher methadone doses (> 60 mg) reported larger cocaine effects after single doses on several measures including ratings of Liking and Stimulated. Finally, the opiate symptom scores after cocaine administration were 100% larger than those observed previously after cocaine administration to opiate-experienced, but not dependent, individuals. These data suggest that any improvement in cocaine abuse observed in methadone-maintained individuals is not related to a blocking of the subjective effects of cocaine, and that higher methadone doses could have a negative impact on cocaine abuse in some individuals.