In a 6-week double blind non-crossover study, trazodone and imipramine have been compared in the treatment of patients with severe endogenous depression. By random allocation, 13 patients entered each treatment group. The mean maintenance dosage of trazodone was 300 mg (range 200-350 mg) and of imipramine 160 mg (range 150-175 mg). Some evidence is presented to suggest that trazodone may have an earlier anxiolytic effect than imipramine by day 4 and a greater antidepressant effect by day 22 of treatment. Apart from the frequency of impaired visual accommodation being significantly greater in the imipramine group, there were no differences between the treatments with respect to side-effects. No abnormalities were found from laboratory investigations and ECG assessments.