During the tenth biennial examination, 1315 Framingham study participants free of cardiovascular disease had fibrinogen measured along with other major cardiovascular risk factors including cigarette smoking. The fibrinogen values were significantly higher in smokers than in nonsmokers, increased with the amount smoked in each sex, and exsmokers had values as low as those of nonsmokers. Over 10 years of follow-up, 165 men and 147 women developed cardiovascular disease, the risk in both sexes increasing progressively in relation to antecedent fibrinogen values over the 180 to 450 mg/dl range. Risk gradients for cardiovascular disease in men diminished with advancing age. In men, risk of cardiovascular disease was related to cigarette smoking. This was true in the multivariate case taking all standard risk factors into account. As for fibrinogen, the impact diminished with advancing age. Regression coefficients were actually larger in the multivariate than in the univariate case because of a negative correlation between smoking and blood pressure. Fibrinogen contributed to cardiovascular disease, risk taking into account both cigarette smoking and other risk factors. When fibrinogen is added to the multivariate model for prediction of cardiovascular disease the coefficient for smoking becomes much reduced and is no longer statistically significant. However, each independently contributed to risk in cross-sectional analysis. These data provide another mechanism whereby cigarette smoking influences the occurrence of atherocardiovascular disease and also another reason for prohibiting cigarette use.