A 51-year-old man was found comatose in a decerebrate posture in a cottage. Brain MRI showed diffuse high-signal-intensity areas in the white matter on T 2-weighted and FLAIR images, and diffusion-weighted images showed marked diffuse high intensity areas in the white matter. Initially inflammatory demyelinating diseases were suspected and methylprednisolone pulse therapy was administered. However, no improvement was noted. On close inspection of the cottage, a gas generator was discovered in the poorly ventilated room. He was therefore suspected to have suffered from gas intoxication, including carbon monoxide (CO). Hyperbaric oxygen therapy was administered, but without any improvement. The diffuse white matter lesions and brain edema progressed with time and the patient died of cerebral herniation. Autopsy revealed no inflammatory processes. Most cases with CO intoxication show hyperintense lesions in the globus pallidus on both sides in T 2-weighted images, and some cases show lesions only in the white matter without any involvement of the globus pallidus. The progressive clinical course, diffuse leukoencephalopathy and brain edema may be due to apoptosis of oligodendrocytes. CO intoxication is thus important in the differential diagnosis of diffuse white matter lesions of the cerebrum.