A brief description is given of the various laboratory and clinical manifestations of immune suppression that arise when strenuous exertion must be carried out in the face of a negative energy balance, shifts of circadian rhythm, sleep deprivation, psychological stressors, and exposure to hostile environments (extremes of heat or cold, high or low ambient pressures, and hyper- or hypo-gravity conditions). From the operational viewpoint, immune suppression could impair both physical and mental performance by increasing susceptibility to opportunistic microorganisms. It is also likely to increase susceptibility to sepsis following trauma or extensive burns, and has occasionally predisposed to fatal myocarditis. The effects of such challenges are complex, in part because of interactions between the various stressors. It is thus important to investigate the impact and to devise appropriate countermeasures with the full physical and intellectual resources of a defense environmental research laboratory. Existing knowledge of the topic is reviewed, and suggestions are made for research that may lead to new and more effective countermeasures.