In preliminary experiments we have found that intraperitoneal administration of the antibiotic polymyxin to rats resulted in a marked decrease in the night-time rise in body temperature. ORal administration of the antibiotics bacitracin and streptomycin reduced both the night-time and day-time body temperature of rats. Gerfree mice have a significant decrease in the magnitude of the night-time rise in body teomperature, compared to conventionally-reared mice. Based on these data, we hypothesize that the absolute body temperature and the daily rhythm in body temperature are in part attributable to endotoxin or other bacterial products originating in the gastrointestinal tract. Studies are outlined in which we will determine whether administration of normal mouse intestinal flora to germfree mice restores the amplitude in their body temperature rhythm; in additon, experiments are outlined to determine the origin of these signals (e.g. form endotoxin, form Gram-positive organism, etc.). Other studies are designed to determine whether the C3H/HeJ mouse (the endotoxin-resistant mouse) has an attenuation in its rhythm in body temperature compared to the C3H/OuJ mouse. In endotoxin or some other bacterial product form the gut afects the rhythm in body temperature, it may be doing so via the protein mediator of fever and other "acute-phase responses," interleukin-1 (IL-1). A series of experiments are outlined to test the hypothesis that IL-1 may vary on a circadian basis, and that this rhythm in IL-1 influences th erhythm in body temperature. It is possible that the host requires some signal (s?) form the intestinal flora for what most believe are "endogenous" set-points (such as temperature), and rhythms in these set-points. Were this the case, then our view towards the commensal relationship that clearly exists between ourselves and our gut flora would be markedly altered.