One hundred and twenty seven patients with major depressive episode were included in a double-blind, four-week, prospective, randomized, multi-centre parallel-group trial comparing moclobemide and imipramine. The dose of moclobemide was 150-525 mg/day and that of imipramine 50-175 mg/day; the mean daily doses during the last week of treatment were 307 mg and 100 mg of moclobemide and imipramine, respectively. The decrease of the total scores of the Hamilton Depression Scale (HDRS) as well as the Overall Assessment of Efficacy by the Investigators showed significant amelioration of depression in both treatment groups (p < 0.001). No significant differences were found between the moclobemide and imipramine groups with regard to treatment outcome. The onset of the antidepressant activity was faster in the moclobemide group as measured by the Assessment of the Investigators. This difference was not observed when the therapeutic index figures calculated on the basis of the changes in the HDRS scores were scrutinized. Treatment-emergent side effects were somewhat more frequent during imipramine than during moclobemide treatment. Nevertheless, a total of only four patients discontinued the trial prematurely because of poor tolerability. Imipramine-treated patients reported more anticholinergic side effects, whereas tiredness and headache were observed more frequently in the moclobemide-treated patients. Restlessness, nervousness and sleep disturbances were noted with equal incidence in both patient groups.