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Psychoneuroimmunology is a relatively new discipline which deals with CNS-immune system interactions. The evidence for such interactions was reviewed, as was the neuroendocrinologic response to stress. Recent evidence indicates that the behavioral, nervous system, and neuroendocrine responses to stress are mediated by hypothalamic CRF, which acts on both the sympathetic nervous system and the HPA axis, resulting in increased levels of corticosteroids, catecholamines, and certain opiates, substances which are generally immunosuppressive. Concentrations of growth hormone and prolactin, which are immunoenhancing, are elevated early during the response to stress but are later suppressed. Although several other neuromediators may also be released with stress, the net effect of a variety of acute stressors is down regulation of the immune system function. In the following minireview, I consider whether stress alters the resistance of the host to infection as well as the immunomodulatory effects of released immune system mediators on the brain.