Although a neuromuscular syndrome has been induced experimentally by vitamin E deficiency, a human syndrome has not yet been documented. This report describes a 7-year-old boy with severe malabsorption since birth who presented with progressive external ophthalmoplegia, proximal muscle weakness, peripheral neuropathy, hyporeflexia, and bilateral Babinski signs. Abnormalities on neurologic examination included elevated creatine phosphokinase and aldolase, slowed distal sensory latencies, type II muscle fiber atrophy, and a plasma vitamin E level of 8 μg per deciliter (normal, 550-1500 μg per deciliter). Treatment with oral water-solubilized vitamin E (400 IU daily; < 50 times the normal daily intake) was begun, with repeat laboratory studies at 3-month intervals. Over a 16-month period, plasma vitamin E content gradually increased to 350 μg per deciliter, associated with declining sarcoplasmic enzyme activities and clinical improvement.