We evaluated the baseline serum levels of beta carotene, total carotenoids, vitamin A and E, and retinol-binding protein among 156 initially healthy men who participated in the Multiple Risk Factor Intervention Trial (MRFIT) and who subsequently died of cancer and 311 controls individually matched for age, smoking status, randomization group, date of randomization, and clinical center. Both total carotenoids and beta carotene levels were lower in the 66 lung cancer cases than in their matched controls. For all cancer deaths combined, there were no significant differences in total carotenoids or beta carotene between cases and controls. The relationship between lower serum carotenoid levels and lung cancer persisted after adjusting for the number of cigarettes, alcohol intake, serum thiocyanate levels, and cholesterol levels in the blood. Serum levels of retinol, alpha tocopherol, and retinol-binding protein were not related to any cancer site. The results of this study provide further evidence for a possible protective effect of beta carotene against lung cancer among cigarette smokers.