In a double-blind, noncrossover study, general practice patients suffering from depression were treated with either trazodone (100–200 mg, nocte) or mianserin (60–120 mg, nocte) for 6 weeks. For entry into the study, a minimum score of 14 on the 17-point Hamilton Depression Rating Scale (HDRS) was necessary. By random allocation, 125 patients (61 on trazodone and 64 on mianserin) entered the study. Altogether there were 43 withdrawals, of whom 31 (72%) had received mianserin. At least one of the reasons for 22 withdrawals from the mianserin group was an unacceptable side effect, frequently being daytime drowsiness. In contrast, only 5 of the trazodone group withdrew because of side effects. These differences in the withdrawal rates for those patients entering the study were statistically significant (p < 0.001). A total of 82 patients completed treatment and entered the analysis for efficacy; 49 on trazodone and 33 on mianserin. Results show that both treatments were equally effective in reducing symptoms of depression and anxiety. Thus, the mean HDRS score was 21.3 and 21.5 for trazodone and mianserin, respectively, at the start of treatment which decreased to 6.2 and 5.9, respectively, at the end of 6 weeks. The mean Zung self-rating anxiety scores for trazodone and mianserin were 45.6 and 44.4 at the start of treatment and 33.6 and 31.1 at the end of the study. The results suggest that, on the basis of fewer significant side effects, trazodone is more acceptable to mianserin in treating depression, with or without anxiety, in general practice patients.