The changes in thermoregulatory effectors produced by an injection of polyriboinosinic acid: polyribocytidylic acid (Poly I:C) or interferon were assessed and compared in control rats, in rats with hypothalamic somatostatin (SS) receptor blockade and in rats with hypothalamic SS depletion. Intrahypothalamic (i.h., 0.05-0.50 μg) or intraperitoneal (i.p., 100-600 μg) administration of Poly I:C caused a dose-related rise in colon temperature in control rats at all ambient temperatures (Ta) studied. A Poly I:C-induced fever was produced by increased metabolism at a Ta of 8 °C, whereas at 30 °C, it was caused by cutaneous vasoconstriction. At a Ta of 22 °C, the fever was caused by increased metabolism and cutaneous vasoconstriction. On the other hand, i.h. administration of SS-14 antagonist (0.1-0.5 ng) caused a dose-related fall in colon temperature at Ta of 8 °C or 22 °C. At a Ta of 8 °C, the hypothermia was caused by decreased metabolism, whereas at 22 °C, it was caused by decreased metabolism and cutaneous vasodilation. At a Ta of 30 °C, the thermoregulatory effectors were not affected by SS-14 antagonist treatment. Furthermore, the fever induced by Poly I:C or interferon was significantly reduced by pretreatment of rats with an i.p. dose of cysteamine (30 mg. kg-1) or an i.h. dose of SS-14 antagonist (0.1 ng). The results indicate that a somatostatinergic pathway in rat hypothalamus may mediate the fever induced by interferon or its inducer Poly I:C. © 1990 Springer-Verlag.