We propose to investigate three areas related to fever and disease: (1) The biology and evolution of fever - In these studies we propose to continue our investigations, which we initiated several years ago, on the characteristics of the febrile responses in the non-mammalian vertebrates. (2) The adaptive value of fever - The function of fever (is fever adaptive or maladaptive?) has not been clearly demonstrated in birds and mammals. Based on our work using lizards, and by others using fish, it appears that fever has survival value in the ectothermic or "cold-blooded" vertebrates. We now plan to investigate the function of fever in birds and mammals. Clearly, if fever has survival value in these vertebrates, then the wide-spread use of antipyretic drugs to reduce moderate fevers must be re-evaluated. (3) The mechanisms behind the adaptive value of fever - Using the ectothermic lizards as our animal model to investigate the effects of fever on various aspects of the immune response, we plan to investigate several possible mechanisms behind the survival value of fever.