During the fall of 1992, 250 (10%) of 2,500 Rambouilet cross feeder lambs grazing Sorghum bicolor developed neurologic signs including weakness, ataxia, head shaking, knuckling of the fetlocks, inability to rise, and opisthotonos. One hundred fifteen (46%) of the affected lambs died. Twenty of the surviving lambs exhibited residual neurologic signs of ataxia when stressed. At the same time, 275 (25%) of 1,100 ewes grazing a nearby sudex pasture (S. sudanese x S. bicolor) gave birth to lambs that were weak and unable to rise. Newborn lambs exhibited extensor rigidity and opisthotonos when assisted to a standing position. The dystocias that occurred were due to lambs with contracted limbs (arthrogryposis). All affected lambs died or were euthanized. Histologic examination of the brains of 3 feeder lambs and 9 newborn lambs revealed similar microscopic lesions. The predominant change was the presence of focal axonal enlargements (spheroids) in the proximal segments of axons, which were restricted to the nuclei of the medulla, cerebellum, and midbrain. In addition, the spinal cord contained spheroids in the ventral horn gray matter of the 6 newborns examined. Ultrastructurally, the spheroids were composed of aggregates of neurofilaments, mitochondria, vesicular bodies, and dense bodies bounded by a thin myelin sheath. There was mild gliosis in the more severely affected animals of both groups. There was minimal Wallerian degeneration in the white matter adjacent to affected nuclei in the brain and the ventromedial and dorsolateral funiculi of the spinal cord. This is the first detailed report of Sorghum toxicity in sheep.