The origin of altered (99m)Tc-HMPAO distribution at SPECT in psychiatric disorders is unknown. Correlations between brain (99m)Tc-HMPAO distribution and muscle succinate-cytochrome c reductase (SCR, complex II + III) were assessed in 20 unmedicated psychiatric patients. Significant negative correlations were found between (99m)Tc-HMPAO distribution in associative sensory regions and SCR activity. Sensory cortices are normally enriched in complex II activity. The production of electrons and reactive oxygen species affecting the redox state is considered to be highest from complex III, but complex II may also contribute. The negative relationship between (99m)Tc-HMPAO uptake and SCR activity may be due to redox state alterations influencing fixation of the radiopharmaceutical.