Six subjects with DSM-III defined unipolar major depressive disorder had positron emission tomography scans using 18F-2-fluoro-2-deoxy-D-glucose (2FDG) before and after treatment with imipramine. Their 12 scans were compared to the scans of six controls matched for age. Significant reductions in metabolism for subjects in the depressed group were found on scans for both the anterior and right frontal regions. significant reductions in metabolism occurred more often in the right hemisphere than the left. No significant changes in metabolism could be attributed to imipramine. In addition, absolute metabolic rates were not related to the degree of depression pre- and post-treatment. The findings suggest that hypometabolism in the frontal cortex and right hemisphere may occur in major depressive disorders.