Use of vitamin and mineral supplements was assessed in a population-based case-control study of oral and pharyngeal cancer, conducted during 1984-1985 in four areas of the United States. There was no association with intake of multivitamin products, but users of supplements of individual vitamins, including vitamins A, B, C, and E, were at lower risk after controlling for the effects of tobacco, alcohol, and other risk factors for these cancers. After further adjustment for use of other supplements, vitamin E was the only supplement that remained associated with a significantly reduced cancer risk. The adjusted odds ratio of oral and pharyngeal cancer for "ever regularly used" vitamin E was 0.5 (95% confidence interval 0.4-0.6). To the authors' knowledge, this is the first epidemiologic study to show a reduced oral cancer risk with vitamin E use. Although it is not clear that the lower risk among consumers of vitamin E supplements is due to the vitamin per se, the findings are consistent with experimental evidence and should prompt further research on the role of vitamin E and other micronutrients as inhibitors of oral and pharyngeal cancer.