Adverse effects of interferon (IFN) treatment are common, and efforts to minimize these reactions are of considerable importance. IFN-&bgr;-1a is an established therapy for patients with relapsing–remitting multiple sclerosis (MS). Its psychiatric side effects are debated and not yet fully established. The authors report here the case of a patient on IFN-&bgr;-1a therapy for MS who developed acute delirium, delusion, and depression that ceased with treatment discontinuation. Although he had a history of recurrent major depressive disorder, his prior psychiatric illness had followed a course that was clinically independent of other signs of MS. This observation points out psychiatric vulnerability of patients taking IFN-&bgr;-1a therapy for MS and suggests that IFN-&bgr;-1a may induce or exacerbate preexisting psychotic symptoms.