The effect of clomipramine hydrochloride in severe obsessive-compulsive disorder (OCD) was compared with that of nortriptyline hydrochloride and placebo in a five-week randomized, double-blind trial. Clomipramine, but not nortriptyline, was superior to placebo in interview-based ratings of severity of OCD. The effect was not clear-cut until after five weeks of treatment. When clomipramine was given openly to 22 patients after the end of the controlled trial, half of the patients responded to the drug. The response could not be predicted from severity or duration of illness, sex or age of the patient, or presence or absence of secondary depressive symptoms. The amelioration with clomipramine was not sustained if the drug was withdrawn.