A 25-year-old woman with multiple sclerosis and an affective disorder probably secondary to MS presented with multiple neurological signs and symptoms suggestive of active MS, most prominently akinetic mutism. Spinal fluid analysis and MRI supported a diagnosis of active MS. SPECT and EEG were nonspecifically abnormal. After 6 weeks of severe akinetic mutism refractory to one ECT treatment and trials of steroids and stimulants, the patient recovered spontaneously over a 2-month period. An acute brainstem lesion seen on MRI may explain this patient's akinetic mutism.