In each of four studies of the human pharmacology of bupropion, 12 healthy volunteers received 6 different treatments, including placebo, at weekly intervals under double-blind conditions. In one study, auditory vigilance and tapping rates improved after d-amphetamine, 5 and 10 mg; were impaired by amitriptyline, 25 mg; but were unaffected by bupropion, 50 and 100 mg. Subjects were drowsy after amitriptyline and more alert and sociable after d-amphetamine; no such changes occurred with bupropion. No changes in pupil size, heart rate, and systolic blood pressure were seen with bupropion. In a second study bupropion, 200 mg, and nomifensine, 100 mg, produced no significant behavioral or autonomic effects. EEG changes occurred after amitriptyline and d-amphetamine but not bupropion. Thus, bupropion at these doses lacked stimulant, anticholinergic, and cardiovascular effects. Bupropion's interactions with diazepam and with alcohol were examined in separate studies. Diazepam, 5 and 2.5 mg, produced drowsiness and impaired auditory vigilance. Bupropion, 100 mg, produced no effect alone but, combined with diazepam, abolished the vigilance impairment and drowsiness seen with diazepam, 2.5 and 5 mg, alone. A similar but less clear-cut pattern was seen with alcohol. Bupropion, 100 mg, had no effect alone but abolished the sedation and auditory vigilance impairment produced by alcohol when co-administered. Interactions between bupropion and the depressant drugs are unlikely to produce clinical problems.