This study examined peripheral catecholamine-O-methyl-transferase (COMT) gene expression in obsessive-compulsive disorder (OCD) patients and healthy controls. Participants included 35 first episode OCD patients and 31 age- and sex-matched healthy controls. Relative COMT gene expression levels were examined by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) in peripheral blood of all the subjects. COMT gene expression levels, normalized by glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were significantly decreased in the OCD group compared with healthy controls (F=6.244, p=0.015). OCD patients showed a 32% down-regulation. We also found lower COMT gene expression levels in female in comparison to male participants (F=5.366, p=0.024) in the sample as a whole. COMT gene expression down-regulation of male OCD patients relative to male controls is 38%, and that of female OCD patients relative to female controls is 27%. These results suggest that COMT gene expression down-regulation might play an important role in the development of OCD and that there may be gender differences in this alteration.