The intestinal barrier is formed by enterocyte membranes, tight junctions, secreted mucus, and immunologic factors, such as tissue macrophages. Dysfunction of this barrier can be caused by different types of stress (e.g., physiological, pathological, psychological, pharmacological) and can lead to increased intestinal permeability. Increased permeability to endotoxin, a component of the walls of gram-negative bacteria, causes local or systemic inflammatory reactions, or both. The immune response(s) can then promote more serious conditions. Exertional heat stroke is an example of such a condition. During severe exercise-heat stress, possibly combined with other stresses, reductions in intestinal blood flow, direct thermal damage to the intestinal mucosa, or both, can cause intestinal barrier disruption and endotoxemia. The resulting inflammatory response is believed to be involved in altered thermoregulation and multiple-organ dysfunction. Possible means for preventing or attenuating, or both, many stress-induced intestinal barrier problems include environmental, pharmaceutical, or nutritional approaches, or a combination of these.