There is evidence that bilirubin functions as an endogenous tissue protector by its antioxidant and anti-complement actions, properties that are relevant to atherogenesis. Serum bilirubin distribution and its relation to cardiovascular risk were examined in 4156 individuals aged 5-30 years from a biracial (black white) community. Bilirubin levels showed significant differences related to race (whites > blacks) and sex (males > females, except in 5-10 year olds). In males the levels increased with age up to 24 years, while in females the changes were less conspicuous. Both adiposity and cigarette smoking associated independently and inversely with bilirubin. In addition, serum bilirubin correlated positively with HDL cholesterol and inversely with triglycerides, VLDL cholesterol, LDL cholesterol, insulin, glucose and systolic blood pressure although these correlations were significant only in certain age-race-sex groups. Offspring with a parental history of heart attack or hypertension had consistently lower bilirubin levels than those without such parental history. Thus, bilirubin may be an inverse risk factor for cardiovascular disease.