OBJECTIVE--To assess the validity of the 1990 US weight guidelines for women that support a substantial gain in weight at approximately 35 years of age and recommend a range of body mass index (BMI) (defined as weight in kilograms divided by the square of height in meters) from 21 to 27 kg/m2, in terms of coronary heart disease (CHD) risk in women. DESIGN--Prospective cohort study. SETTING--Female registered nurses in the United States. PARTICIPANTS--A total of 115,818 women aged 30 to 55 years in 1976 and without a history of previous CHD. MAIN OUTCOME MEASURE--Incidence of CHD defined as nonfatal myocardial infarction or fatal CHD. RESULTS--During 14 years of follow-up, 1292 cases of CHD were ascertained. After controlling for age, smoking, menopausal status, postmenopausal hormone use, and parental history of CHD and using as a reference women with a BMI of less than 21 kg/m2, relative risks (RRs) and 95% confidence intervals (CIs) for CHD were 1.19 (0.97 to 1.44) for a BMI of 21 to 22.9 kg/m2, 1.46 (1.20 to 1.77) for a BMI of 23 to 24.9 kg/m2, 2.06 (1.72 to 2.48) for a BMI of 25 to 28.9 kg/m2, and 3.56 (2.96 to 4.29) for a BMI of 29 kg/m2 or more. Women who gained weight from 18 years of age were compared with those with stable weight (+/- 5 kg) in analyses that controlled for the same variables as well as BMI at 18 years of age. The RRs and CIs were 1.25 (1.01 to 1.55) for a 5- to 7.9-kg gain, 1.64 (1.33 to 2.04) for an 8- to 10.9-kg gain, 1.92 (1.61 to 2.29) for an 11- to 19-kg gain, and 2.65 (2.17 to 3.22) for a gain of 20 kg or more. Among women with the BMI range of 18 to 25 kg/m2, weight gain after 18 years of age remained a strong predictor of CHD risk. CONCLUSIONS--Higher levels of body weight within the "normal" range, as well as modest weight gains after 18 years of age, appear to increase risks of CHD in middle-aged women. These data provide evidence that current US weight guidelines may be falsely reassuring to the large proportion of women older than 35 years who are within the current guidelines but have potentially avoidable risks of CHD.