This 6-week, double-blind, randomised, multicentre study was performed to assess the efficacy and tolerability of evening administration of 150 mg trazodone as an initial and maintenance therapy and to compare this reomen with recommended dosages of mianserin, dothiepin and amitriptyline in the treatment of depressed, adult, general practice patients. A total of 227 eligible depressed patients were recruited into the study by a panel of general practitioners. One hundred and twelve patients were randomised to receive trazodone therapy, 36 received mianserin, 35 received dothiepin and 44 received amitriptyline. Trazodone was administered as a single daily dose of 150 rag. Mianserin was given at a dose of 30 mg for the first 7 days followed by 60 mg daily for the remaining 5 weeks. Dothiepin and amitriptyline were both given at a dosage of 75 mg daily for the 1st week; this was then increased to 150 mg and 100 rag, respectively, for the final 5 weeks of the study. Efficacy of the four treatments was assessed using the modified Hamilton depression rating scale scores and by the Investigator's judgment of both the global severity and improvement of the condition. No significant differences were shown, using any measure of efficacy, between trazodone and any of the three comparatot drugs. All treatments resulted in significant improvement in both Ham-D scores and global measures over the period of the study. Using a total side-effect score to assess the incidence and severity of adverse events and adjusting for baseline differences, the four treatments were found to differ. Trazodone was associated with a lower incidence of dry mouth, visual disturbance and drowsiness than amitriptyline, and a lower incidence of dizziness/faintness than mianserin. All four treatments were associated with improvements in sleep quality and ease of getting to sleep. Trazodone and dothiepin were of greatest benefit and mianserin was of least benefit in this respect.