This study was designed to compare the antidepressant effects of minaprine and amitriptyline in a group of 60 outpatients suffering from a major depressive episode as defined by the DSM III. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with flexible daily doses of 200-300 mg of minaprine and 50-75 mg of amitriptyline. Both drugs showed significant global antidepressant efficacy with no significant difference between the two treatment groups. The Hamilton item 'psychomotor retardation' improved earlier with minaprine than amitriptyline. The incidence of anticholinergic adverse effects was significantly higher in the amitriptyline treatment group.