Bilateral reductions in the volume of the anterior cingulate cortex have been reported in patients with major depressive disorder (MDD) when compared with findings in healthy controls. We compared regional brain volumes in the subgenual prefrontal cortex (SGPFC; Brodmann area (BA) 24(sg)), subcallosal gyrus (BA25) and paracingulate gyrus (BA32) in healthy control subjects and a large and well-characterized sample of patients with recurrent MDD, all of whom had received extensive antidepressant therapy. Patients with a remitted episode of MDD had SGPFC volumes larger than those of healthy controls, while those in an active illness episode did not differ from controls. There were no differences in subcallosal gyrus and paracingulate gyrus volumes between patients with MDD and healthy controls, with the exception that women with MDD had smaller paracingulate volumes than their sex-matched controls. This effect was not related to duration of illness, number of previous episodes, age at illness onset, or age at the time of scanning. Our findings demonstrate SGPFC volume increases in association with long-term antidepressant therapy and suggest that this result may be linked to positive clinical response.