Following perineural capsaicin pretreatment of the main trunks of the abdominal vagus of rats, the first and the second phases of the polyphasic febrile response to intravenous lipopolysaccharide were unaltered, while the third phase of fever course (peak at 5 h) was attenuated. In rats desensitized by intraperitoneal (i.p.) capsaicin (i.e. abdominal non-systemic desensitization), mainly the first but not the later fever phases were reduced. The postprandial hyperthermia to intragastric injection of BaSO4 suspension was attenuated by either i.p. or perineural capsaicin treatment. It is concluded that, in contrast to the accepted model of postprandial hyperthermia, which is mediated by capsaicin-sensitive fibers of the abdominal vagus, in the early phase of polyphasic fever the vagal afferent nerves appear to play no role. The influence of i.p. capsaicin-desensitization on this initiating fever phase is independent of the vagus, and a capsaicin-induced alteration of endotoxin action in the liver, prior to vagal nerve endings, is more likely. The late febrile phase is probably influenced by efferent vagal fibers, which might be damaged more easily by perineural than i.p. capsaicin treatment.