We report the results of a multicenter, double-blind study conducted in a general practice setting, in which the efficacy and tolerability of moclobemide, a new antidepressant drug of the reversible inhibitor of monoamine oxidase type A class, were compared with those of maprotiline, a noradrenaline reuptake inhibitor often prescribed in the general practice setting. Participating general practitioners were required to make differential diagnoses of depressive disorders according to DSM-III criteria and then quantitatively assess the efficacy of treatment using the Hamilton Depression Rating Scale (HDRS) and the Zung self-rating depression scale (Zung SDS). One hundred thirty outpatients (mean age 48 years) with major depression according to DSM-III were randomized to receive either moclobemide 300 mg or maprotiline 75 mg daily for 4 weeks. From day 8, dosages were increased if necessary up to a maximum of 400 mg of moclobemide or 100 mg of maprotiline. The results showed that moclobemide was as effective as maprotiline (HDRS, Zung SDS); moclobemide appeared to have the same antidepressant and anxiolytic activity, but a stronger drive-enhancing effect. Moclobemide was the better-tolerated drug, producing fewer side effects than maprotiline did: in particular, fewer instances of somnolence and dry mouth. The good tolerability of the compound was confirmed by the qualitative assessments of the study physicians.