It remains a tragic event that some 10 000 individuals in Japan developed a unique neurologic disease, subacute myelo-optico-neuropathy (SMON). Many of the affected patients still suffer serious sequelae, such as dysesthesia and muscle weakness in the lower extremities, and loss or deficits in visual acuity. Neuropathologic studies on SMON patients and experimental reproduction of the disease in animals which had been administered clioquinol helped resolve the etiology of this disease. Common pathologic features seen in SMON patients and in dogs and cats chronically intoxicated with clioquinol were distal dominant axonopathy, mainly in the spinal long tracts and optic tracts. Particular abdominal symptoms present in patients after clioquinol ingestion could also be reproduced experimentally in dogs. SMON research in Japan may be worth reviewing for determining the etiology and preventing similar neurotoxic diseases in the future.