Risk factors for first nonfatal myocardial infarction (MI) in women younger than age 50 years were evaluated in a case-control study of 255 women with MI and 802 controls. The relative risk of MI increased with the amount smoked. The estimated risk of MI for current smokers of 35 or more cigarettes per day was ten times that of women who never smoked; an estimated 65% of MIs were attributable to cigarette smoking. The relative risk of MI increased markedly with increasing levels of total plasma cholesterol and decreasing levels of high-density lipoproteins, and the effects of the two factors appeared to be independent. Other factors significantly associated with MI were hypertension, angina pectoris, diabetes mellitus, blood group A, and a history of MI or stroke before age 60 years in a mother or sibling. Factors not significantly associated with MI were obesity, history of preeclamptic toxemia, and type A personality. Women who were postmenopausal appeared to have a lower risk of MI than premenopausal women of similar ages. Of the identified risk factors, the most prominent was cigarette smoking, a habit that is amenable to change.