Studies were undertaken to evaluate the effects of exercise on the development of pancreatic cancer. Exercise is one life-style factor that has received little attention with regard to its role in the etiology of cancer. Male Lewis and female F344 rats were initiated with azaserine during the suckling period and weaned to the experimental protocols. Food and water were available ad libitum. A purified diet of 20% unsaturated fat was fed to both the sedentary and exercise groups. Rats of the exercise group had free access to voluntary exercise wheels. At approximately 2 and 4 months postinitiation, pancreases were evaluated for the number and size of azaserine-induced putative preneoplastic foci by quantitative stereology. Voluntary exercise activity peaked at approximately 2 months postinitiation with a gradual decline in activity there-after. Male Lewis rats averaged 0.95 +/- 0.13 km/day (SE) and female F344 rats averaged 2.73 +/- 0.26 km/day of voluntary wheel running. Compared with the sedentary groups, male Lewis and female F344 rats with access to the running wheels had significantly smaller foci at 4 months postinitiation. Azaserine-induced foci were evaluated in the male Lewis rats at both 2 and 4 months postinitiation. At 4 months postinitiation, the size and growth rate (as measured by [3H]thymidine autoradiography) of foci were less in the rats with access to the exercise wheels. No differences were observed at 2 months postinitiation. Access to voluntary exercise reduced the growth rate of azaserine-induced pancreatic foci. The effect occurred late in the postinitiation phase and was not directly related to the extent of running activity early in the postinitiation phase.