Recent studies have reported that patients with unipolar major depression may show a lower whole brain cerebral blood flow (CBF) and reduced regional CBF in frontal, temporal, and parietal lobes. The present study used single photon emission computed tomography (SPECT) with the CBF marker Tc-99m-hexamethylpropyleneamineoxine (HMPAO) to measure the cortical CBF of six individual regions of interest (ROIs), total ROI, and left or right hemispheric total ROI in 43 unipolar depressed subjects and 12 normal control subjects. There were no significant differences in the distribution of Tc-99m-HMPAO uptake into total ROI, right or left global ROI, prefrontal, motor frontal, parietal, temporal, visual cortex, or associative visual cortex between patients with melancholic depression, simple major depression, or minor depression and healthy control subjects. There were also no significant differences in the right-left distribution of uptake between the patients and the control subjects. Hypoperfusion was observed in motor frontal and parietal cortex of patients who had been taking benzodiazepines during the study period. It is concluded that cortical CBF, as assessed with Tc-99m-HMPAO SPECT, is relatively intact in the present sample of patients with severe depression.