Two horse farms, on which there was a high incidence of proven and suspected equine degenerative myeloencephalopathy (EDM), were studied. Symmetric ataxia and paresis, along with laryngeal adductor, cervicofacial, local cervical, and cutaneous trunci hyporeflexia, characterized the syndrome. Serum vitamin E concentration reflected a deficient state in affected and unaffected horses on both farms when compared with selected reference groups and with published values. A high incidence of the disease was evident in offspring of two particular sires on one farm. Vitamin E supplementation resulted in correction of the deficient state in most horses and was associated with a drastic reduction in the incidence of EDM on one farm from 40% to less than 10% the year following vitamin E supplementation. In addition, during the last year, the severity of signs in the few cases was dramatically reduced. This information substantiates the hypothesis that EDM is a vitamin E-responsive disorder of Equidae with a possible familial predisposition.