Angiographic evidence of coronary artery disease (CAD) was correlated with leukocyte count (WBC), red cell count (RBC), cigarette smoking, age, sex, and cholesterol and triglyceride concentrations in 573 patients who underwent coronary arteriography and who did not have evidence of infection or recent myocardial infarction. Smokers had a higher WBC (7,449 +/- 1,964 leukocytes/mm3 vs 6,533 +/- 1,557, p = 0.0001) and RBC (4.921 X 10(6) +/- 0.491 X 10(6) erythrocytes/mm3 vs 4.753 X 10(6) +/- 0.480 X 10(6) p = 0.0001) than nonsmokers. Patients with CAD had a higher WBC (7,280 +/- 1,926 vs 6,664 +/- 1,700, p = 0.0005) and RBC (4.903 X 10(6) +/- 0.488 vs 4.777 X 10(6) +/- 0.485 X 10(6), p = 0.0062) than those with normal coronary arteriograms. A positive correlation between WBC and the severity of CAD (sum of arterial diameter narrowing) was noted (r = 0.16, p = 0.0001). Multiple regression showed an independent contribution of WBC in predicting severity of CAD (F = 9.26, p = 0.0025), after accounting for the effects of age, sex, serum cholesterol and triglyceride levels. When smoking was entered into the equation, the contribution of WBC in predicting the severity of angiographic CAD became weaker (F = 4.46, p = 0.035). Similar relations were seen when only smokers were analyzed and when patients with history of remote myocardial infarction were excluded. In nonsmokers these associations became either insignificant or much weaker. Thus, the relation of WBC, and RBC with CAD is mainly due to the elevation of WBC and RBC and the increase of CAD risk induced by cigarette smoking.