1. The purpose of this study was to investigate the effect of the intraperitoneal (I.P.), intravenous (I.V.) or intrapreoptic area (POA) injection of prostaglandin E2 (PGE2) on the body temperature of restrained and unrestrained rats. The effect of I.P. PGE2 on the body temperature of rats during fever induced by I.P. injection of interleukin-1 beta (IL-1 beta) was also investigated. 2. Prior to injection, restrained rats had body temperatures of approximately 1 degree C higher than unrestrained rats. The I.P. injection of PGE2 (0.05 and 0.5 mg kg-1) caused body temperature to fall towards the pre-restraint levels in a dose-dependent manner. This fall in body temperature was preceded by a sharp increase in tail skin temperature that was also dependent on dose. The I.P. injection of PGE2 had no effect on the body temperature of unrestrained animals. 3. The I.V. injection of PGE2 caused very little change in the body temperature of restrained rats. However, when injected I.V. into unrestrained animals, PGE2 caused dose-dependent fevers. The injection of PGE2 (50 ng) into the POA resulted in fever in both restrained and unrestrained animals. 4. The I.P. injection of IL-1 beta (10 micrograms kg-1) caused a biphasic fever that lasted at least 420 min. The I.P. injection of PGE2 180 min after the injection of IL-1 beta caused a transient decrease in the rats' body temperature. This drop in body temperature was not associated with a decrease in metabolic rate. 5. These data support the hypothesis that during restraint stress hyperthermia and IL-1 beta fever, the I.P. injection of PGE2 acts peripherally to lower the body temperature of rats.