Magnetic-resonance morphometry performed on 72 patients with major depression compared with 38 control subjects replicated previously reported, statistically significant reductions in the volumes of the caudate (P < 0.03) and putamen (P < 0.05) in depressed patients. Borderline statistical significance was observed for whole-brain (P < 0.07) and frontal volume (P < 0.10) in a subsample of 32 patients matched on age and sex with 32 control subjects, whereas statistical significance was observed for the full sample (P < 0.007 and P < 0.03, respectively). Chronological age was related to volume of the frontal lobes (P < 0.0002), caudate (P < 0.0001), putamen (P < 0.008), thalamus (P < 0.002), cerebellum (P < 0.007), lateral ventricles (P < 0.0001), and ratios of [whole brain]/[whole brain + cerebrospinal fluid (CSF)] (P < 0.0001) and [frontal]/[frontal + CSF] (P < 0.0001). Age of first depressive episode was related to putamen volume after accounting for chronological age (R2= 0.16, P < 0.005), and a correlation of 0.26 (P < 0.04) was observed between caudate volume and global mental status. Results are in accord with previous reports of basal-ganglia abnormalities in depressed patients and support the role of subcortical structures in mediating affective disorder.