OBJECTIVE The brain regions that are critically involved in the pathophysiology of anorexia nervosa have not been clearly elucidated. Moreover, decrease in cerebral tissue during extreme malnutrition has been demonstrated repeatedly in anorexia nervosa, but data regarding the reversibility of this cerebral tissue decrease are conflicting. The authors examined region-specific gray matter changes and global cerebral volumes in recovered patients with anorexia nervosa. METHOD High-resolution, T1-weighted magnetic resonance imaging (MRI) and voxel-based morphometry were performed in 22 recovered women with anorexia nervosa and in 37 healthy comparison women. Recovery was defined as a body mass index above 17.0 kg/m(2) and regular menses for at least 6 months. RESULTS The global volumes of gray matter (but not white matter) were decreased in patients with anorexia nervosa by approximately 1%. Analyses of region-specific gray matter changes revealed a gray matter decrease bilaterally in the anterior cingulate cortex of approximately 5%, which remained significant after correction for global effects. This gray matter decrease correlated significantly with the lowest body mass index of lifetime but not with other clinical variables. CONCLUSIONS In anorexia nervosa, part of the global gray matter loss persists over the long run. Region-specific gray matter loss in the anterior cingulate cortex is directly related to the severity of anorexia nervosa, indicating an important role of this area in the pathophysiology of the disorder. Further research is warranted to determine the cause, specificity, and functional consequences of this structural brain change in anorexia nervosa.