Bilirubin, the primary end product of heme catabolism, is a key marker of liver and hematological disorders, and important cytoprotective properties have been ascribed to this bile pigment. The Third National Health and Nutrition Examination Survey, a comprehensive assessment of health and nutrition in the United States, was analyzed to determine the demographics and correlates of serum bilirubin levels in the general population. Men and women aged 17 and older were included in the weighted analysis, representing a total of 176,748,462 subjects. The mean serum total bilirubin in the adult population is 0.62 +/- 0.003 mg/dL (SEM), with a 97.5% cut-off of 1.4 mg/dL. Serum bilirubin levels are significantly higher in men (0.72 +/- 0.004) than in women (0.52 +/- 0.003 mg/dL) and are lower in non-Hispanic blacks (0.55 +/- 0.005 mg/dL) compared with non-Hispanic whites (0.63 +/- 0.004 mg/dL) and Mexican Americans (0.61 +/- 0.005 mg/dL). Bilirubin concentrations are unrelated to body weight but are reduced in active smokers. Individuals with a history of nondermatological malignancy exhibit significantly lower serum bilirubin concentrations compared with those who do not have a history of nondermatological cancer. In particular, each 1-mg/dL increase in serum bilirubin is associated with a markedly decreased prevalence of colorectal cancer (OR = 0.257; 95% CI 0.254-0.260). In conclusion, serum bilirubin levels vary significantly with gender, race, and smoking status. The observed inverse correlation between serum bilirubin concentrations and a history of nondermatological malignancy, particularly colorectal cancer, warrants further investigation of a potentially important chemopreventive function of bilirubin.