Exposure to acute or chronic stress (mental or physical) is associated with an increase in disease susceptibility and severity. Evidence suggests that stress alters disease processes by modulating the immune system. Given the health problems associated with repeated acute and chronic stressor exposure, it is important to develop treatments which could prevent the immunologically deleterious consequences of stressor exposure. A simple pharmacological approach is currently unrealistic because the complex neurohormonal mediators of stress-induced changes in immune function are not understood. Another approach would be to develop a behavioral intervention that would buffer the deleterious consequences of stress, and thereby contribute to an overall improvement in health. Preliminary data from the applicant's laboratory suggest that regular, moderate, physical activity is a successful intervention capable of having such an effect. Regular, moderate exercise is associated with improved overall health. The health benefits of physical exercise are both direct and indirect. Regular, moderate exercise, for example, is associated with a decrease in coronary heart disease and high blood pressure, probably due to direct improvements in cardiovascular function. In addition to a reduction in heart disease, regular, moderate exercise is also associated with a decrease in bacterial and viral illness, which could be due to the indirect health benefits of exercise, i.e., stress reduction. Thus, it is possible that the reported reduction in infectious disease associated with exercise is due to the prevention of stress-induced suppression of the immune system. Using a well established animal model of stress, the applicant investigated the effect of acute stressor exposure on the development of a specific antibody response to a benign protein, keyhole limpet hemocyanin (KLH). Measurement of specific antibody levels in the blood after challenge with KLH provides and excellent measure of the in vivo immune response and the cellular mechanisms are well understood. Thus, using this well characterized stress and immunity paradigm, the applicant presents evidence that regular, moderate, exercise can prevent the effect of stress on anti-KLH antibody. The goal of this research proposal, therefore, is to better characterize the protective effect of regular, moderate physical activity on the detrimental immunological consequences of acute stressor exposure.