Objective: To assess the regional cerebral perfusion changes in patients with major depressive illness, with or without suicidal behavior by 99mTcHMPAO brain perfusion SPECT. Methods: 99mTc HMPAO brain SPECT was performed in 40 subjects including 10 controls in Group A. There were 30 patients with major depression meeting the DSM-IV criteria scoring > 17 on the Hamilton Rating Scale. The patients were subclassified into groups B and C. Group B included 16 patients suffering from major depression. Group C included 14 patients with major depression and attempted suicide or who had moderate to severe suicidal risk as assessed by Intent Score Scale. Semiquantitative assessment of cerebral perfusion was perfromed through a brain quantification software program. The cortextocerebellum ratios were calculated in 16 ROIs drawn on coronal section in all the patients. Results: The scintigraphic evaluation of the cerebral perfusion in the Group B (nonsuicidal) showed significant hypoperfusion in the prefrontal (p < 0.001), orbitofrontal (p < 0.01), frontal motor (p < 0.01) and the temporal lobes (p < 0.01). In the Group C (suicidal), significant hypoperfusion was noticed in the prefrontal (p < 0.001), orbitofrontal (p < 0.01) and frontal motor areas (p < 0.001). The temporal lobe showed hyperperfusion (p < 0.001). Conclusion: In major depressive illness, the prefrontal, the orbitofrontal and the frontal motor areas, are markedly hypoperfused. In severe depression not associated with any suicidal behavior, there is hypoperfusion in the temporal lobes, whereas the temporal lobes are hyperperfused in suicidal behavior, with the degree of hyperperfusion related to the severity of the suicidal behaviour.