Single photon emission computed tomography (SPECT) brain imaging with 123I labeled iofetamine (IMP) has been used to study several neuropsychiatric disorders. However, little attention has been given to patients with major depression. In the present study IMP SPECT images were obtained on 19 depressed patients and 12 medical comparison subjects who had no focal abnormalities on MRI or CT scans. 5 mCi of 123I IMP was administered intravenously and SPECT images were obtained using a GE Starcamm 2000 SPECT system. After standard reconstruction of the images, an automated region of interest (ROI) computer program was applied to each tomographic brain image. Coronal images were then used to analyze lateralized differences in IMP activity. Measurements were made of the mean IMP activity per pixel, the maximum activity per pixel, and the ratio of the mean activity per pixel in the ROI to that of the cerebellum. On visual inspection, 12 out of 19 depressed patients (63%) and only of 12 medical comparison patients (8%) appeared to have substantially increased IMP activity in the right temporal lobe (P less than 0.005). But semi-quantitative analysis showed that while IMP activity was greater in the right than the left temporal lobe of depressed patients (P less than 0.0001), it was also present in medical comparison patients (P less than 0.01). Although there was no difference in the frequency of asymmetry between groups, it was more pronounced in depressed patients. These data suggest that asymmetric temporal lobe activity on IMP SPECT images may be of potential diagnostic utility in some patients with affective disorders.