After a week on a thiamine-free diet and daily injections of pyrithiamine hydrobromide, a group of rats began to lose weight; soon thereafter hypothermia, piloerection, and ataxia developed, followed by convulsions and death. Neuropathologic examination disclosed hemorrhagic necrotic lesions in the thalamus, hypothalamus, collicular plate, vestibular nuclei, and inferior olives. The control groups did not show neurologic signs or neuropathologic abnormalities. The lesions in thiamine-deficient rats were similar in character and distribution to those of human Wernicke's disease. Because this experimental regimen produces neuropathologic changes rapidly and consistently, this animal model should be useful in studies designed to examine the pathophysiologic aspects of experimental Wernicke's disease in particular and CNS thiamine deficiency in general.