Forty-one patients completed a four-week double-blind study comparing dothiepin and amitriptyline. The anti-depressant effect of the two drugs was measured by the Hamilton depression rating scale and a five-point global scale. Side-effects were recorded as mild, moderate or severe. Analysis of the results failed to demonstrate a statistically significant difference between the anti-depressant effect of the two drugs, but dothiepin was the favoured therapy in all assessments. Both drugs produced a significant improvement (p < 0·01) after only one week's therapy. The incidence and severity of side-effects were much less with dothiepin. An unexpected difference in the Hamilton scores at the end of the fourth week is to be investigated further.