We have not encountered any brain single-photon emission tomography (SPET) study performed in adolescent depressed patients in the literature. Therefore, we used technetium-99m hexamethylpropylene amine oxime (Tc-99m-HMPAO) brain SPET in adolescent patients with major depressive disorder (MDD) to examine the possible changes in cerebral perfusion a.nd the possible association between perfusion indices and clinical variables. Fourteen adolescent out-patients (nine females, five males; mean+/-SD age: 13.11+/-1.43 years; range: 11-15 years) fulfilling the DSM-IV criteria for MDD and 11 age-matched healthy control subjects (six females, five males; mean+/-SD age: 13.80+/-1.60 years; range: 12-15 years) were included in the study, Tc-99-HMPAO brain SPET was performed twice in the patient group and once in the control group. The first SPET investigation was per formed under non-medicated conditions and the second was performed after depressive symptoms had subsided. A relative perfusion index (PI) was calculated as the ratio of regional cortical activity to the whole brain activity. We found significant differences between the PI values of the untreated depressed patients and those of the controls, indicating relatively reduced perfusion in the left anterofrontal and left temporal cortical areas. No significant differences in regional PI values were found between the remitted depressed patients and the controls. Our study suggests that adolescent patients with MDD may have regional cerebral blood flow deficits in frontal regions and a greater anterofrontal right-left perfusion asymmetry compared with normal subjects. The fact that these abnormalities in perfusion indices have a trend toward normal values with symptomatic improvement suggests that they may be state-dependent markers for adolescent MDD.