We examined the effects of intravenous (IV) or intracerebro-ventricular (ICV) injection of prostaglandin E2 (PGE2) on the rectal temperature of restrained rats. The IV injection of PGE2 (0.5 mg/kg) caused hypothermia in rats with high initial rectal temperatures, but caused an elevation in rectal temperature in those animals whose starting temperatures were low. In contrast, the ICV injection of PGE2 induced fever, regardless of the rectal temperature at the time of injection. We also examined whether temperature changes due to the IV injection of endotoxin (lipopolysaccharide, LPS, 10 micrograms/kg) or interleukin-1 beta(IL-1 beta, 0.2 micrograms/kg) were dependent upon the rats' initial rectal temperatures. Rats with low rectal temperatures developed fevers in response to LPS, while animals with high starting temperatures showed hypothermia. In contrast, the IV injection of IL-1 beta produced fever regardless of initial rectal temperature. These data suggest that PGE2 acts centrally to cause fever and peripherally to cause hypothermia, and that following the injection of LPS, these opposing actions of PGE2 may act together to determine the thermoregulatory response.