The relation of oral contraceptive (OC) use to the risk of hospitalization for myocardial infarction (MI) was evaluated among 121,964 US nurses who responded to a mail questionnaire. There were 156 women who reported having been hospitalized for MI before the menopause, and 23 (15%) were OC users at the time of the MI. Of 3120 controls matched to the cases for menopausal status at the time of the MI and for age, 304 (10%) were using OCs at the time of the MI. The apparent increase in the risk of MI for current OC users was not explained by cigarette smoking, hypertension, elevated cholesterol or other identified risk factors for MI. We estimated that OC use increased MI risk 1.8-fold overall and 2.8-fold among nonsmokers without other risk factors. The increase in risk attributable to the combined effect of current OC use, cigarette smoking and hypertension was considerably greater than what would be predicted from the sum of the separate effects of these factors.