In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.