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The mammalian response to stress involves the release of soluble products from the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Cells of the immune system respond to many of the hormones, neurotransmitters, and neuropeptides through specific receptors. The function of the immune system is critical in the mammalian response to infectious disease. A growing body of evidence identifies stress as a cofactor in infectious disease susceptibility and outcomes. It has been suggested that effects of stress on the immune system may mediate the relationship between stress and infectious disease. This article reviews recent psychoneuroimmunology literature exploring the effects of stress on the pathogenesis of, and immune response to, infectious disease in mammals.