To investigate the possible relationship between dietary factors and the development of multiple primary cancer, a nested case-control study was carried out within a cohort of 1,090 oral and pharyngeal cancer patients. This patient group, enrolled in 1984-1985 in a population-based case-control study conducted in four areas of the United States, was followed up through June 1989 for the occurrence of second primary cancer. Information on a number of risk factors, including diet, ascertained from interviews conducted at baseline (1984-1985) and at follow-up were compared between 80 patients with histologically confirmed second primary cancers (39% in the upper aerodigestive tract, 32% in the lung, 29% elsewhere) and 189 sex- and survival-matched control patients free of second cancers. Although few significant trends emerged, the results were suggestive of a protective effect provided by higher intake of vegetables. Risk of second primary cancers was 40-60% lower among those with the highest levels of intake for total vegetables and most vegetable subgroups, including dark yellow, cruciferous, and green leafy vegetables and legumes. Risks were also nonsignificantly lower among those with high consumption of vitamin C and carotenoids, with the adverse effects of alcohol being most evident among heavy drinkers with low vitamin C or carotenoid intake. There was also some evidence of an interaction between smoking and vitamin C consumption, but numbers of nonsmokers were small. Among other dietary factors considered, positive associations were found with increasing consumption of meats, liver, and retinol. The findings suggest that dietary factors contribute along with alcohol and smoking to the excess risks of second primary cancers among patients with oral and pharyngeal cancers.