Depressed patients in general practice were included in a double-blind placebo-controlled six-week trial of amitriptyline (median dose 125 mg). The patients were relatively mildly ill and satisfied diagnostic criteria for depression and treatment with antidepressants in routine practice. Amitriptyline was found to be considerably superior to placebo after six weeks and significantly so as early as two weeks after the start of treatment. The effects of the antidepressant were on the core symptoms of depression, and were apparent in all but the most mildly ill patients. The findings suggest that tricyclic antidepressants are of considerable therapeutic benefit to depressed patients in general practice.