Cigarette smoking is clearly associated with increased risk of atherosclerotic disease, but the mechanisms underlying the association are not known. In the direction of increasing the risk of atherosclerotic disease, smokers have more extensive advanced atherosclerosis, slightly higher serum concentrations of total cholesterol and LDL cholesterol, slightly lower concentrations of HDL cholesterol, higher erythrocyte counts and hemoglobin concentrations, and higher fasting blood-glucose concentrations than do nonsmokers. In the direction of decreasing risk, smokers are leaner and have lower blood pressures than nonsmokers. Observed effects which also may augment atherosclerosis in smokers as compared to nonsmokers include leucocytosis and increased hepatic mixed function oxygenase activity. This review of available evidence indicates that cigarette smoking probably contributes to atherosclerotic disease by a variety of mechanisms. © 1979.