The clinical efficacy and adverse reaction profile of bupropion, an atypical antidepressant, was compared with the tricyclic imipramine in 63 elderly depressives. Patients were randomly assigned to treatment with 150 or 450 mg/day of bupropion, 150 mg/day of imipramine, or placebo for 35 days. Both doses of bupropion were equivalent to imipramine in antidepressant efficacy. The higher dose of bupropion had a more rapid onset of effect than the low dose and significantly greater anxiolytic activity than either imipramine or the lower dose. Both doses of bupropion had adverse reaction profiles strikingly similar to placebo and, in marked contrast to imipramine, did not produce sedation or anticholinergic side effects. Cognition improved equally in all groups. It was concluded that bupropion has therapeutic advantages over the tricyclics in the treatment of elderly depressives.