Moderate and heavy exercise induce a multitude of changes in the neuroendocrine immune system, the net effects of which depend on various other factors including the host's physical condition, and the intensity and duration of the exercise bout. Most investigators report that the risk of upper respiratory infection is increased following heavy exertion, but is decreased after moderate exercise. Many heavy exercise-induced changes in the host's immune defenses are consistent with the alterations reported in classical stress studies; some consensus has been achieved in this area that heavy exertion may indeed elicit responses common to psychological forms of stress. The immunomodulation consists, most notably, of shifts in the number and function of circulating innate and adaptive immune cell populations apparently in response to the release of classical stress hormones and cytokines, and expression of selectin and adhesin molecules. Rapid trafficking of cells in and out of the blood compartment in response to exertion probably mirrors the demand for certain cell types in specific tissues, a hypothesis requiring verification in animal models and ultimately the human. Also needed are studies correlating the functional status of the circulating cells with those in the tissues.