Clinical observations and laboratory experiments have suggested a role for testosterone in the development of prostatic cancer. Since physical training may act to lower testosterone levels, men who are very active may have a reduced risk of this cancer. To test this hypothesis, the authors prospectively followed 17,719 Harvard alumni (aged 30-79 years) from 1965 or 1969 to 1977, and 1980 to 1988 for the occurrence of prostatic cancer (n = 419). Physical activity was assessed in either 1962 or 1966, and again in 1977, based on self-reported stair climbing, walking, and sports played. Alumni who expended greater than 4,000 kcal/week at both assessments were at reduced risk of developing prostatic cancer (age-adjusted rate ratio, 0.12; 95% confidence interval 0.02-0.89) compared with their inactive counterparts who expended less than 1,000 kcal/week at both assessments. These results should be interpreted cautiously, since only one case of prostatic cancer was identified among alumni highly active at both assessments, who contributed 4% of total person-years to the analysis. Among alumni aged 70 years and older, those who extended greater than 4,000 kcal/week at either assessment had about half the risk of those who expended less than 1,000 kcal/week at either assessment (age-adjusted rate ratio, 0.53; 95% confidence interval 0.29-0.95). The authors attribute these findings to the increased precision with which physical activity could be measured when combining two activity assessments. Alternatively, long-term maintenance of a high level of physical activity may be necessary for further reduction of risk. There was no evidence of a dose-response relation.