A number of studies have used magnetic resonance imaging to examine the volumetric differences in temporal lobe structures especially the hippocampus in patients suffering from major depressive disorder (MDD). Although some studies reported lower hippocampal volume, others did not. It is proposed that the inconsistency among studies may be due to the heterogeneity of patients and antidepressant treatment during scanning. In this study, we aimed to evaluate the hippocampus in drug-free patients. Twenty-four patients (6 males and 18 females) diagnosed as having MDD according to the DSM-IV criteria and 24 healthy controls (6 males and 18 females) were included in the study. Eleven of the patients had their first mood episode and were drug-naïve. Other patients were drug-free for at least 4 weeks. The Hamilton depression rating scale (HAM-D) assessed the severity of depression. Magnetic resonance imaging was performed on a 1.5-T MR unit. The Cavalieri method of modern design stereology in conjunction with point counting was used to estimate hippocampal volume. The data were evaluated by a repeated measure of ANOVA and the intracranial volume was taken as a covariate. A significant hippocampal volume difference was observed between the patients and healthy controls (F=4.43, df=1.45, P<0.05); however, laterality had no effect on the volumes (F=0.03, df=1.45, P>0.05). The left hippocampus of patients was significantly lower than those of controls (t=1.98, df=46, P<0.05). Correlation analysis showed a correlation between HAM-D scores and the right hippocampal volume. The results of this study indicate that hippocampus volume is reduced in depressed patients especially in the left side. This finding in the drug-free depressed outpatients without a history of alcohol dependence supports previous studies that have reported lower hippocampal volume.