We prospectively examined the incidence of coronary heart disease in relation to cigarette smoking in a cohort of 119,404 female nurses who were 30 to 55 years of age in 1976 and were free of diagnosed coronary disease. During six years of follow-up, 65 of the women died of fatal coronary heart disease and 242 had a nonfatal myocardial infarction. The number of cigarettes smoked per day was positively associated with the risk of fatal coronary heart disease (relative risk = 5.5 for greater than or equal to 25 cigarettes per day), nonfatal myocardial infarction (relative risk = 5.8), and angina pectoris (relative risk = 2.6). Even smoking 1 to 4 or 5 to 14 cigarettes per day was associated with a twofold to three-fold increase in the risk of fatal coronary heart disease or nonfatal infarction. Overall, cigarette smoking accounted for approximately half these events. The attributable (absolute excess) risk of coronary heart disease due to current smoking was highest among women who were already at increased risk because of older age, a parental history of myocardial infarction, a higher relative weight, hypertension, hypercholesterolemia, or diabetes. In contrast, former smokers had little, if any, increase in risk. These prospective data emphasize the importance of cigarette smoking as a determinant of coronary heart disease in women, as well as the markedly increased hazards associated with this habit in combination with other risk factors for this disease.