Vitamin E deficiency is often associated with symptoms of a peripheral neuropathy. To evaluate whether vitamin E deficiency affects the vitamin E content of the peripheral nervous system, we measured the alpha-tocopherol content in biopsy specimens of sural nerve and adipose tissue from 5 patients with symptomatic vitamin E deficiency (2 with homozygous hypobetalipoproteinemia and 3 with familial isolated vitamin E deficiency) and 34 control patients with neurologic diseases without vitamin E deficiency. A significant reduction in tissue tocopherol content was present in the vitamin E-deficient patients, as compared with the controls, both in sural nerves (1.8 +/- 1.2 vs. 20 +/- 16 ng per microgram of cholesterol [P less than 0.001], or 7.7 +/- 5.4 vs. 64 +/- 44 ng per milligram of wet weight [P less than 0.01]) and in adipose tissue (46 +/- 43 vs. 222 +/- 111 ng per milligram of triglyceride [P less than 0.001]). Levels of tocopherol in adipose tissue were significantly correlated (P less than 0.001) with levels in peripheral nerves. The low tocopherol content of the nerves preceded histologic degeneration in three vitamin E-deficient patients, suggesting that the nerve injury resulted from the low nerve tocopherol content.