Patients with multiple sclerosis (MS) frequently develop psychiatric disturbances. The clinical histories and magnetic resonance imaging results from eight patients with MS and psychiatric disorders were compared with those from eight control MS patients matched for age, sex, duration and severity of illness, and clinical course. Both groups had widespread lesions on the magnetic resonance imaging scans; however, the psychiatric group had more clinically defined sites of MS involvement, possibly indicating a difference in the biologic activity of the lesions in this group. The total lesion area was not different between the groups. However, the distribution of lesions did differ; the psychiatric group had significantly more temporal lobe involvement than the control group. These results indicate a role for the cerebral lesions themselves, particularly those in the temporal lobes, in the genesis of psychiatric disorders in MS.