Temporal lobe dysfunction may be involved in mediating some of the symptoms associated with depression. The purpose of this study was to compare temporal lobe activity during depression with activity during clinical improvement in the same patient using SPECT brain imaging with [I123]-labeled iofetamine (IMP). Five patients with major depression who had pretreatment IMP SPECT scans were re-imaged during clinical recovery. Regions of interest were drawn around the temporal poles on the coronal sections of SPECT images, as well as around the whole brain on the sagittal sections. The count rates of IMP activity were then compared before and during clinical recovery. In all cases, we observed a normalization in the degree of right temporal lobe IMP accumulation (i.e., temporal lobe asymmetry) during successful antidepressant therapy. Depression 3:213-211 (1995/1996). © 1996 Wiley-Liss, Inc.