This review describes how exercise and physical training affect the immune system. Although many immune functions are stimulated by moderate physical activity, more vigorous effort and periods of heavy training suppress various immune response parameters. Experimental studies from our own laboratories and elsewhere illustrate that cellular infiltration of the active muscle is accompanied by phagocyte activation, suppressed NK-cell function, impaired lymphocyte proliferation, decreased in-vitro immunoglobulin production, pro-inflammatory eicosanoid release, cytokine cascade activation, and altered expression of cytokine receptors. Examples cover deliberate heavy training; single bouts of fatiguing, submaximal work; repeated bouts of exercise; and ultra-long distance athletic events. In young adults, age, environment, and light physical training do not change immune-response parameters. Parallels between immune impairment after vigorous exercise and reactions to surgical sepsis are noted. Vigorous exercise probably induces subclinical muscle injury and an associated inflammatory response. Heavy exercise may be a useful experimental model for developing more effective treatments for sepsis. For protection average athletes may take the anti-oxidant vitamins C and E and non-steroidal inflammatory drugs, if the muscles show signs of an inflammatory reaction. Top-level athletes have received immunoglobulin preparations.