We examined the concentrations of five carotenoids in the serum and diet of a population-based sample of 400 individuals to determine what physiologic and lifestyle factors were related to serum carotenoid concentrations, how these relationships differed among the carotenoids, and if these relationships reflected differences in carotenoid intake. Lower serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein+zeaxanthin generally were associated with male gender, smoking, younger age, lower non-HDL cholesterol, greater ethanol consumption and higher body mass index. Serum lycopene generally was not related to these factors, but lower lycopene levels were associated with older age and lower non-HDL cholesterol. Only the hydrocarbon carotenoids (alpha- and beta-carotene and lycopene) were directly associated with HDL cholesterol. The associations of some factors (gender, age, smoking, and ethanol intake) with serum carotenoids were similar to the associations of these factors with levels in the diet, indicating that serum carotenoids may reflect the influence of these factors on carotenoid intake. Consistent with this notion, correlations between serum and dietary carotenoids did not differ between smokers and nonsmokers. Other factors (HDL and non-HDL cholesterol and body mass index) associated with carotenoids in the serum were not associated with carotenoid intake, indicating that physiologic conditions that affect the absorption, storage, and utilization of carotenoids may influence these associations. These physiologic and behavioral correlates of carotenoids could explain or modify associations of carotenoids with chronic diseases.