This was a multicentre, double-blind, randomised, parallel-group study which was performed to assess the tolerance and efficacy of administration of 150 mg trazodone nocte as an initial and maintenance therapy compared with a 50 mg t.d.s. regimen. Particular attention was paid to the incidence of adverse events and to the effect of treatment on sleep over the 6-week period of the study. A total of 182 eligible, depressed patients were recruited into the study by a panel of 24 general practitioners. Eighty-seven patients were randomised to receive 50 mg trazodone three times a day and 95 to receive 150 mg trazodone as a single evening dose. Efficacy of the two treatment regimens was assessed using the modified Hamilton depression rating scale scores and by the Investigator's judgement of both the global severity and improvement of depression. The mean HAM-D scores of the two treatment groups were found not to be significantly different. There was strong evidence that the scores decreased over the 6-week trial period and that the rate of this decrease was different for the two study groups. For measures of both current global severity and improvement, no significant treatment differences were revealed. The changes in Hamilton scores occurring during the study period were found to be equal in the two treatment groups. Using a total side effects score to assess the incidence and severity of adverse events, the two dosing regimens were found not to be significantly different. After 1 week of therapy, volunteered side effects ratings indicated that the 150 mg o.d. treatment was associated with a higher incidence of dizziness, faintness and a dry mouth. Overall, the nocte regimen caused a higher incidence of relatively milder effects compared with the divided dose regimen. The mean scores of the Leeds Sleep Questionnaire indicated that the 150 mg nocte dose produced greater benefit in ease of getting to sleep and quality of sleep during the 1st few weeks of treatment, although this difference between treatments did not reach significance. Changes in ease of awakening and feelings after waking were found to be greater during therapy with 50 mg trazodone administered three times a day than when the medication was taken in a single dose. During the first 2 weeks of therapy, reductions in middle and delayed insomnia as rated on the HAM-D scale were greater when trazodone was given as a single 150 mg evening dose than as 50 mg t.d.s.