A disease with striking clinical and pathologic similarities to the spongiform encephalopathies is described in six Rocky Mountain elk (Cervus elaphus nelsoni) maintained in wildlife facilities in Colorado and Wyoming. Clinical signs included behavioral alterations and progressive weight loss over a period of weeks or months. Consistent microscopic lesions were limited to the central nervous system and characterized by widespread spongiform transformation of the neuropil, intracytoplasmic vacuoles in neuronal perikaryons, and astrocytic hypertrophy and hyperplasia.