The modifying influence of individual risk factors on the relation between myocardial infarction (MI) and cigarette smoking was evaluated in a case-control study of women younger than 50 years of age. Data from 555 women who survived first MIs were compared with those of 1,864 hospital controls of similar ages. The risk of MI increased with the number of cigarettes smoked, both in the presence and absence of factors that predispose to an infarction. In particular, the association was apparent at all ages, at all levels of total serum cholesterol and high-density lipoprotein cholesterol, and in the presence and absence of oral contraceptive use, hypertension, diabetes mellitus, blood group A, tendency to type A behavior, and family history of MI. The relative increase in risk was generally greater the lower the underlying predisposition to MI. There was clear evidence, however, that recent oral contraceptive use substantially augmented the increased risk for smokers, and hypercholesterolemia may have had the same effect.