Amoxapine, a tricyclic dibenzoxazepine is an antidepressant which in the dosage range of 150-300 mg/day is notable for its rapid onset of action. Because of the rather long, approximately 30-hour, half-life of 8-hydroxyamoxapine, the active metabolite of amoxapine, the possibility was raised that amoxapine therapy may be carried out with single daily dosages. Such a dosage schedule may improve compliance and, if appropriately timed, decrease perception of some of the unwanted effects of the drug. To test the hypothesis that there may be no disadvantages and perhaps even advantages of a once-a-day regimen as compared to a divided dosage schedule, a 6-week double-blind clinical trial was carried out in 35 hospitalized patients with major (18 patients) and minor (17 patients) depressive disorders. While no statistically significant difference was found in overall therapeutic and adverse effects between the groups treated with single or divided daily doses, onset of therapeutic effect appeared a bit faster in the group treated with single daily doses. Of particular relevance for drugs which can be given in single daily doses is their effect on psychomotor performance tests. In view of the findings that a once-a-day dosage regimen with amoxapine may have advantages over divided daily doses, a second study was carried out in which the effects of amoxapine (50 and 100 mg) were compared to an inactive placebo and amitriptyline (50 mg) with and without ethanol in 8 normal male volunteers. The study was double-blind and followed a latin square design. Since the effects of amoxapine on motor reflex, visual-motor coordination and depth perception did not differ significantly from placebo, the results suggest that the effects of amoxapine on the performances measured are clinically insignificant. No significant interaction with ethanol was noted.