The relationship between plasma carotenoids, plasma cholesterol, cigarette smoking, vitamin supplement use, and intakes of alcohol, vitamin A, and carotene were investigated in 1981 for 187 Multiple Risk Factor Intervention Trial men in Pittsburgh. The total plasma carotenoid value was positively correlated with the dietary carotene and vitamin A indices (estimated by a food frequency questionnaire), vitamin A supplement usage, and plasma cholesterol, and inversely related to cigarette smoking, alcohol intake, and serum aspartate transaminase. The mean plasma carotenoid level was higher in nonsmokers (means = 186 micrograms/dl, 95% confidence interval (CI) 178-195) as compared with cigarette smokers (means = 164 micrograms/dl, 95% CI 151-178) and in vitamin A supplement users (means = 206 micrograms/dl, 95% CI 188-224) as compared with nonusers (means = 172 micrograms/dl, 95% CI 164-179). Variables associated with the total plasma carotenoids in multiple regression analyses included dietary vitamin A and carotene, calorie intake, weekly alcohol intake, cigarette smoking, vitamin supplement usage, and plasma cholesterol, and accounted for 27% of the variance. The total plasma carotenoid value was also highly correlated with plasma beta-carotene (r = 0.67) and lycopene (r = 0.68). The mean beta-carotene (30 micrograms/dl), however, accounted for only 16% of the total plasma carotenoids.