Twenty-eight patients with a major depressive episode previously investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, were followed up at an interval of 9-28 months with the same investigation after full recovery. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Sixteen patients were scanned when optimally matched for drug treatment (4) or on both occasions drug free (12). The other 12 patients were fully recovered but could not be matched for drug status; these patients showed significantly more retardation, diurnal mood variation and guilt at presentation. Significant bilateral increases in tracer uptake were confined to basal ganglia and inferior anterior cingulate cortex in the matched group, where there were additional increases in thalamus and posterior cingulate cortex on the right side. There were no statistically discernible changes in the neocortex in the matched sample. The unmatched sample yielded inconclusive evidence of increased tracer uptake in left temporal cortex. The findings give a potential focus to the neuropharmacological analysis of depressive illness because the topography of the state change in brain function implicates dopamine function.