A 5-year-old, female llama (Lama glama) developed acute, progressive neurological disease, characterized by recumbency, muscle fasciculations, intermittent convulsions/opisthotonos, and absent menace responses. Postmortem histopathologic lesions, limited to the cerebral cortex, consisted of necrosis of the superficial and deep laminae. The clinical disease and microscopic lesions were consistent with polioencephalomalacia.