This study sought to examine the association between cigarette smoking and serum bilirubin antioxidant concentrations in 715 middle-aged men undergoing coronary angiography. The study involved 153 current smokers, 251 who quit smoking and 311 who never smoked. Serum bilirubin concentrations were divided into the following quartiles; 0.20-0.57, 0.58-0.73, 0.74-0.95 and 0.96-3.26 mg/dl. The percentage of individuals within each quartile were as follows; current smokers (42, 22, 24, 12), former smokers (22, 27, 23, 28), nonsmokers (16, 28, 27, 29). A total of 42% of the current smokers had bilirubin concentrations in the lowest quartile compared to 16% of the nonsmokers. Also, 12% of the current smokers had bilirubin concentrations in the highest quartile compared to 29% in the nonsmoking group. The Mantel-Haenszel chi-square test for association between ordered categorical variables was 30.6 (P < 0.0001). Subdividing the subjects according to maximum percent stenosis on angiography (< 10, 10-49, 50-100%) revealed a significant inverse association between smoking and bilirubin (< 0.01) within each subset. The data shows that smoking is associated with decreased serum bilirubin concentrations. In addition, it supports the hypothesis that cigarette smoking may increase the risk of coronary artery disease by lowering antioxidant concentrations and raising oxidized lipid and lipoprotein concentrations.