The pathogenesis of fever in man begins with the production of endogenous pyrogen by phagocytic leukocytes in response to exogenous pyrogens (toxic, immunologic or infectious agents). Endogenous pyrogen, a protein, is released from a variety of phagocytic leukocytes and enters the circulation after new messenger RNA and protein are synthesized. Fever is caused by an interaction of endogenous pyrogen with specialized receptors on or near thermosensitive neurons in the thermoregulatory center of the anterior hypothalamus. This interaction may cause local hypothalamic production of prostaglandins, monoamines and, possibly, cyclic AMP. From the anterior hypothalamus, information is transmitted through the posterior hypothalamus to the vasomotor center, which directs sympathetic-nerve fibers to constrict peripheral vessels and decrease heat dissipation.