The efficacy and tolerance of trazodone in the treatment of mixed affective disorder was compared with that of dothiepin in a double-blind, parallel group study in 228 general practice patients at 10 centres. After satisfying entry criteria, patients were randomized to receive either 150 mg trazodone at night, or 75 mg dothiepin at night for a 6-week period. Efficacy was assessed using the Hamilton Rating Scales for Depression and Anxiety. Significant improvements were observed in the condition of patients in each of the two treatment groups during the 6-week treatment period (p = 0.0001), with no statistically significant difference between the groups. There were no marked differences between the two treatment groups in the type of side-effects reported in response to open questioning, although a higher percentage of symptoms in the trazodone group were mild compared to the dothiepin group, and a lower percentage were severe. The incidence side-effects recorded by means of a checklist of common psychotropic side-effects was similar for the two treatment groups: dry mouth and drowsiness were the most frequent. A slightly higher proportion of patients withdrew from the dothiepin group, and of those who withdrew a higher percentage was due to side-effects than in the trazodone group.