Despite the problems of interpreting epidemiological studies and the difficulty in developing appropriate animal models, there is growing evidence that moderate habitual physical activity can protect against certain types of neoplasm, particularly tumors of the colon and the female reproductive tract. Exercise programs also appear to have a beneficial influence on clinical course, at least in the early stages of the disease. Recent demonstration of exercise-induced changes in the activity of macrophages, natural killer cells, lymphokine activated killer cells, neutrophils, and regulating cytokines suggest that immuno-modulation may contribute to the protective value of exercise. Depression of immune function, such as in HIV infection and in old age, is associated with an enhanced susceptibility to tumors; but the sites of tumorigenesis in HIV infection are not those that gain protection from physical activity. Further research is thus needed before it can be asserted that favorable exercise-induced changes in immune function have a material influence on the risks posed by various types of cancer.