A growing body of evidence indicates that physical activity is protective against breast cancer. In 1996-97, we conducted a 15-year follow-up of 5398 college alumnae comprised of former college athletes with their non-athletic classmates. Participants completed a detailed mailed questionnaire on their health history from 1981-82 to the present. Excluding women who had died and non-deliverable questionnaires, 84.7% (n = 3940) of the participants in our earlier study responded to the questionnaire; the response rate for former athletes was 86.6% (n = 1945), for non-athletes, 83.0% (n = 1995). Results confirmed our earlier findings. Based on self-reports, former college athletes had a significantly lower risk of breast cancer than the non-athletes. The OR for the 15-year incidence of breast cancer is 0.605 with 95% confidence interval (CI) (0.438-0.835); the 15-year incident breast cancers were 64 among the athletes and 111 among the non-athletes. Among women under 45 the protective effect of physical activity on the risk of breast cancer is considerably greater; odds ratio (OR) = 0.164, 95% CI (0.042-0.636). Athletic activity during the college and pre-college years is protective against breast cancer throughout the life span, and more markedly among women under 45. These results confirm our earlier findings and the findings of other investigators.