THE role of the amygdala in major depression was investigated. Resting regional cerebral metabolic rate (rCMR glu) was measured with [18 F] fluorodeoxyglucose positron emission tomography (PET) in two samples of subjects using two different PET cameras. The samples consisted of 10 and 17 medication-free depressives and 11 and 13 controls, respectively. Using coregistration of PET and magnetic resonance images, regions were individually delineated for the amygdala and thalamus, the latter of which was used as a control region. Within the depressed groups, right amygdalar rCMR glu was positively correlated with negative affect. Thalamic rCMR glu was not related to negative affect, and amygdalar rCMR glu accounted for a significant portion of variance in depressives' negative affect scores over and above the contribution of thalamic rCMR glu.