The amygdala is believed to be highly relevant to the pathophysiology of obsessive-compulsive disorder (OCD) given its prominent role in fear conditioning and because it is an important target of the serotonin reuptake inhibitors (SRIs), the pharmacotherapy of choice for OCD. In the present study, we measured in vivo volumetric changes in the amygdala in pediatric patients with OCD following 16 weeks of monotherapy with the selective SRI, paroxetine hydrochloride. Amygdala volumes were computed from contiguous 1.5 mm magnetic resonance (MR) images in 11 psychotropic drug-naive patients with OCD prior to and then following treatment. Eleven healthy pediatric comparison subjects also had baseline and follow-up scans, but none of these subjects received medication. Patients demonstrated significant asymmetry of the amygdala (L>R) prior to pharmacologic intervention in contrast to healthy comparison subjects who showed no asymmetry at the time of their baseline scan. Mixed model analyses using age and total brain volume as time varying covariates indicated that left amygdala volume decreased significantly in patients following treatment. The reduction in left amygdala volume in patients correlated significantly with higher paroxetine dosage at the time of the follow-up scan and total cumulative paroxetine exposure between the scans. No significant changes in either right or left amygdala volume were evident among healthy comparison subjects from the baseline to the follow-up scan. These preliminary findings suggest that abnormal asymmetry of the amygdala may play a role in the pathogenesis of OCD and that paroxetine treatment may be associated with a reduction in amygdala volume.