Ten unmedicated and ten medicated patients with major depression and ten controls were investigated with IBZM-SPECT. The ten unmedicated patients were reinvestigated after treatment with tricyclic antidepressants. Dopamine D2 receptor occupancy was not different between patients and controls, or medicated and unmedicated patients. IBZM binding was increased in four patients with psychomotor retardation. Antidepressant therapy led to a decrease in IBZM binding in the five improved patients. Dopamine D2 receptor binding remained unchanged in nonresponders. It is concluded that striatal dopamine D2 receptor binding is not changed in depression or by tricyclic antidepressants; however, it is affected by psychomotor activity. The changes observed might be the result of increased tonic dopamine release in the basal ganglia, but several other explanations exist.