Trichotillomania, an irresistible impulse to pull out one's own hair, is a chronic psychiatric illness that causes severe discomfort, interferes with daily activities, and leads to social isolation. Treatment is usually unsatisfactory. Thirteen women with severe trichotillomania completed a 10-week double-blind, crossover trial of clomipramine, a new tricyclic antidepressant agent with selective antiobsessional effects, and desipramine, a standard tricyclic antidepressant. Treatment with clomipramine resulted in significantly greater improvement in symptoms than desipramine, as indicated by physicians' ratings of the women's clinical progress on a scale in which lower scores indicate improvement (mean [+/- SD] scores: at base line, 10.0; after desipramine treatment, 8.7 +/- 2.4; after clomipramine treatment, 4.7 +/- 3.1; P = 0.006) and by scores on a trichotillomania-impairment scale, in which higher scores indicate greater impairment (at base line, 6.8 +/- 1.7; after desipramine treatment, 6.2 +/- 1.7; after clomipramine treatment, 4.2 +/- 2.7; P = 0.03). The severity of symptoms (mean base-line score, 15.9 +/- 3.8) was reduced more by clomipramine (10.6 +/- 6.4) than by desipramine (14.4 +/- 3.9). The patients reported that the compulsion decreased in intensity and that they were more able to resist the urge to pull out their hair during treatment with clomipramine. We conclude that clomipramine appears to be effective in the short-term treatment of trichotillomania.