BACKGROUND Several lines of evidence suggest that brain dopamine function may contribute to some obsessive-compulsive (OC) phenomena. The effects of catecholamine depletion were examined in drug-free patients with obsessive-compulsive disorder (OCD). METHODS The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT) and diphenhydramine hydrochloride (placebo) were administered for three consecutive days, one week apart, to 6 drug-free adult OCD patients without a personal or family history of chronic tics, in a double-blind, randomized design. The effects of AMPT and placebo on OC, depression, anxiety and global clinical symptoms were assessed. RESULTS AMPT produced no clinically or statistically significant change in any behavioral ratings, including OC symptom severity, compared with placebo. CONCLUSIONS Acute reduction of catecholamine levels does not seem to affect OC symptoms in drug-free patients with OCD. Studies of catecholamine depletion with AMPT in patients with comorbid OCD and chronic tics may be of considerable neurobiological and clinical interest.