Two double-blind four-way crossover studies are reported, comparing the antidepressant effect of 14-day courses of: viloxazine, viloxazine with a tranquillizer either perphenazine or diazepam or tranquillizer alone, against a placebo. In one study the antidepressant effect of viloxazine at a dose of 150 mg daily was statistically greater than that of placebo, whilst in the second study viloxazine was statistically superior to diazepam (15 mg daily). In depressed patients with a clear anxiety component, viloxazine alone seemed preferable to a combination with a tranquillizer as such a combination did not produce an enhanced clinical effect and the incidence of side-effects was possibly increased. Viloxazine was generally well tolerated and side-effects, when they occurred, were generally a mild upper gastro-intestinal disturbance.