HMPAO-single photon emission computerized tomography (SPECT) is a useful technique in studying cerebral blood flow (CBF). This method is suitable to evaluate the differences of CBF with reference to total sleep deprivation (TSD) within 24 h because of the short half-life of the radiopharmaceutical compound. In the present study, CBF before and after TSD was analysed in patients suffering from major depression. The morning before and after TSD, Tc-HMPAO-SPECT was performed in 20 patients. Hamilton Rating Scale for Depression scores and subjective ratings were obtained daily. Eleven patients responded to TSD; 9 were nonresponders. The main finding was a significant left temporal and mainly right parietal increase of CBF, which was observed in the responders only. CBF values and the severity of depression correlated inversely.