The authors investigated whether there were differences in caudate and lenticular nucleus volumes in depressed patients relative to comparison subjects, and whether differences in basal ganglia volume were associated with treatment response to fluoxetine. Brain magnetic resonance images were obtained from 38 unipolar depressed patients and 20 matched comparison subjects. Patients were divided into groups of 'responders' and 'non-responders' based on change in the 17-item Hamilton Depression Rating Scale (HDRS) score after a 10-week open trial of fluoxetine, 20 mg/day. There were no group mean differences in caudate and lenticular nucleus volumes between patients and comparison subjects. Female treatment responders tended to have larger caudate nucleus volumes than male 'responders', and also larger right caudate nucleus volumes than their female 'non-responder' counterparts. Baseline HDRS scores correlated negatively with left caudate nucleus volume in depressed patients. Thus, in mild to moderately depressed patients, we were unable to find differences in caudate and lenticular nucleus-gray matter volumes relative to comparison subjects. One possible reason is that caudate nucleus-gray matter volume and severity of depression are inversely correlated, suggesting that severity of depression may be an important covariate when comparing caudate volumes in depressed patients and control subjects.