Serotonin reuptake inhibitors appear to be uniquely effective treatments for obsessive-compulsive disorder (OCD). This double-blind, placebo-controlled study was the first trial to assess the efficacy of the most selective of the serotonin reuptake inhibitors, citalopram, in OCD. A total of 401 patients were randomized to receive citalopram 20, 40 or 60 mg/day or placebo for 12 weeks. All three doses of citalopram were significantly more effective than placebo measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) change score (P < 0.01). The highest response rate, defined as 25% improvement in Y-BOCS entry score, was observed in the 60 mg group (65%). This compared with 52% and 57.4% in the 40 mg and 20 mg groups. Response rate on placebo was 36.6% (P < 0.05 for all three doses of citalopram compared to placebo). There was no significant difference between the individual doses of citalopram. An advantage was seen for citalopram on the Sheehan Disability Scale compared with placebo (P < 0.05 on all three citalopram groups versus placebo for both the work situation and the family life and home responsibilities and P < 0.05 on citalopram 60 mg and 20 mg versus placebo for the social life and home activities). Citalopram was well tolerated; only 4 to 6 patients in each dose group discontinued the study prematurely due to adverse events.