Current concepts on the pathogenesis of fever emphasize the importance of the cytokine-prostaglandin cascade. This humoral line mediates nonthermal signals to the brain, while the thermal signals supply feedback from the thermoreceptors. However, the humoral line cannot alone account for the whole febrile response. Here, we hypothesize that, besides this humoral mediatory mechanism, nonthermal neural signals of abdominal origin conveyed mainly by the vagus nerve are also important pro-pyretic factors. The pro-pyretic mechanisms are proposed to be in a dynamic balance with endogenous antipyretic mechanisms that also form an integral part of the normal reaction to pyrogens. Further, it is hypothesized that the role of such neural and humoral signals either for elevation or depression of body temperature is not limited to fever but has an important role also in nonfebrile thermoregulation.