We previously demonstrated that direct administration of interferon (IFN) or its inducer polyriboinosinic acid:polyribocytidylic acid [poly(I:C)] into the hypothalamus caused dose-dependent fever in rabbits. It was not clear whether the fever induced by intrahypothalamic injection of poly(I:C) was due to stimulation of IFN or prostaglandin E-2 synthesis in the hypothalamic tissues. Therefore, in the current experiments, we used an established model in which rabbit hypothalamic minces or brain cells were incubated in vitro with poly(I:C) to test for the ability of poly(I:C) to stimulate IFN or PGE-2 synthesis. The results showed that poly(I:C) stimulated PGE-2, but not IFN, synthesis in the hypothalamus. Thus, it appears that the fever induced by poly(I:C) is not related to IFN synthesis in the hypothalamus.