Few studies have examined whether activity and adiposity levels typical of American women affect their risk of ovulatory disorder infertility, and none has examined moderate and vigorous intensity exercise separately. We investigated these associations in the Nurses' Health Study II, comparing prospectively collected data on adiposity and activity for 830 cases of incident ovulatory infertility and 26,125 pregnancies. We observed a U-shaped association between body mass index (BMI) and relative risk of ovulatory infertility, with increased risk for BMI below 20.0 or above 24.0 kg/m2. On the basis of the BMI distribution of U.S. women, these findings suggest that 12% (95% confidence interval = 7-20%) of ovulatory infertility in the U.S. may be attributable to underweight (BMI <20.0) and 25% (95% CI = 20-31%) to overweight (BMI > or = 25.0). An increase in vigorous activity (but not moderate activity) was associated with reduced relative risk of ovulatory infertility. Each hour per week of vigorous activity was associated with a 7% (95% CI = 4-10%) lower relative risk of ovulatory infertility. After adjustment for BMI, a 5% (95% CI = 2-8%) reduction in relative risk per hour of weekly activity remained. These data suggest that, among American women, more ovulatory infertility is attributable to overweight and a sedentary lifestyle than to underweight and overexertion.