A 63-year-old man who developed episodes of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) twice in the course of multiple sclerosis (MS) is reported. SIADH in this patient occurred only during the administration of antibiotics (sulbactam/cefoperazone, SBT/CPZ). At autopsy, demyelinating lesions in the optic nerves, cervical and thoracic spinal cord, and areas adjacent to the lateral ventricles were observed. Destruction and loss of neuronal cells were found in the supraoptic nuclei. Lymphocytic infiltration was observed in the area adjacent to the supraoptic nuclei. Destruction and swelling of axons and reactive astrocytic gliosis were observed in the hypothalamus. SIADH associated with MS is rare and the histological findings in such a case have not yet been reported. It is suggested that the development of SIADH in MS may be related to the damage in the supraoptic nuclei of the hypothalamus.