Functional brain correlates of remission in patients with major depressive disorder (MDD) are measured with positron emission tomography (PET) and 18F-fluorodeoxyglucose. Glucose metabolism was measured in patients (n = 41) with moderate to severe MDD during acute depression and in the remitted state defined as a period of asymptomatic condition over 12 weeks. Data analyses used a region-of-interest (ROI) approach and statistical parametric mapping (SPM). There were significant decreases in metabolism upon remission with respect to the baseline scan in left prefrontal, anterior temporal and anterior cingulate cortex and bilateral thalamus (SPM analysis) and bilateral putamen and cerebellum (SPM and ROI analyses). There was a significant asymmetry in prefrontal and anterior cingulate cortex metabolism with lower metabolism in the left hemisphere that persisted despite clinical remission. These findings support the hypothesis that selective monoamine reuptake inhibition leads to an attenuation of a brain circuit that mediates depressive symptomatology.