To investigate the relationship between serum micronutrients and the subsequent risk of oral and pharyngeal cancer, a nested case-control study was conducted within a cohort of 25,802 adults in Washington County, MD, whose blood samples were collected in 1974 and stored at -70 degrees C for subsequent assays. The serum levels of nutrients in 28 individuals who developed oral and pharyngeal cancer during 1975 to 1990 were compared with levels in 112 matched controls. Serum levels of all individual carotenoids, particularly beta-carotene, were lower among subjects who developed oral and pharyngeal cancer. The risks of this malignancy decreased substantially with increasing serum level of each individual carotenoid. Persons in the highest tertile of total carotenoids had about one-third the cancer risk as those in the lowest tertile. High serum levels of alpha-tocopherol also were related to a low oral cancer risk in later years, but the risks were elevated significantly with increasing serum levels of gamma-tocopherol and selenium. The findings from this study are consistent with many previous epidemiological investigations of dietary factors for oral and pharyngeal cancer and provide further evidence for the potential role of carotenoids and alpha-tocopherol in the chemoprevention of these malignancies.