We investigated the effect of intravenous injection of human recombinant interleukin-1 beta (IL-1) on rectal temperature and prostaglandin E2 concentration in venous and arterial blood and in the push-pull perfusate in the third ventricle of rabbits. Changes in plasma prostaglandin E2 concentration in blood obtained from the marginal ear vein paralleled changes in body temperature during both monophasic and biphasic fevers. The plasma concentration of prostaglandin E2 in blood obtained from the jugular vein increased during the first phase of the biphasic fever. However, no increase in the prostaglandin E2 level in the carotid arterial blood was observed during the biphasic fever. The levels of prostaglandin E2 in the push-pull perfusate in the third ventricle were markedly elevated during both monophasic and biphasic fevers. Intracarotid infusion of prostaglandin E2 did not produce a fever nor result in a change in the prostaglandin E2 concentration of the push-pull perfusate in the third ventricle. The present results suggest that prostaglandin E2 from the blood circulation does not contribute to fever production in rabbits.