Gepirone is a serotonin (5-hydroxytryptamine, 5-HT) type1A receptor agonist and a pharmacologic analogue of buspirone. Two double-blind, placebocontrolled studies show the efficacy of gepirone in the treatment of major depression. Study 1 demonstrates gepirone's superiority over placebo in an 8-week acute treatment of patients with major depression, including the melancholic subtype. Gepirone's antidepressant dose range is tentatively established at 5-30 mg/day. Study 2 reveals the benefit of gepirone compared with placebo in 4-week continuation therapy of patients with major depression who initially responded to 6 weeks of open therapy with gepirone. Analysis of Hamilton Rating Scale for Depression item scores show gepirone especially improves scores on items of core depression.