Obesity is an established risk factor for non-insulin-dependent diabetes mellitus (NIDDM). Anthropometric measures of overall and central obesity as predictors of NIDDM risk have not been as well studied, especially in women. Among 43,581 women enrolled in the Nurses' Health Study who in 1986 provided waist, hip, and weight information and who were initially free from diabetes and other major chronic diseases, NIDDM incidence was followed from 1986 to 1994. After adjustment for age, family history of diabetes, smoking, exercise, and several dietary factors, the relative risk of NIDDM for the 90th percentile of body mass index (BMI) (weight (kg)/height (m)2) (BMI = 29.9) versus the 10th percentile (BMI = 20.1) was 11.2 (95% confidence interval (CI) 7.9-15.9). Controlling for BMI and other potentially confounding factors, the relative risk for the 90th percentile of waist: hip ratio (WHR) (WHR = 0.86) versus the 10th percentile (WHR = 0.70) was 3.1 (95% CI 2.3-4.1), and the relative risk for the 90th percentile of waist circumference (36.2 inches or 92 cm) versus the 10th percentile (26.2 inches or 67 cm) was 5.1 (95% CI 2.9-8.9). BMI, WHR, and waist circumference are powerful independent predictors of NIDDM in US women. Measurement of BMI and waist circumference (with or without hip circumference) are potentially useful tools for clinicians in counseling patients regarding NIDDM risk and risk reduction.