1. Febrile responsiveness of rabbits and rats to intravenous (I.V.) or intracerebroventricular injection of human recombinant interleukin-1 alpha (IL-1 alpha), human recombinant interleukin-1 beta (IL-1 beta) and prostaglandin E2 was examined. 2. The I.V. injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.05-2.0 micrograms/kg. A small dose of IL-1 alpha (0.5 micrograms/kg) or IL-1 beta (0.5 micrograms/kg) produced a monophasic patterned fever in both rabbits and rats. A large dose (2.0 micrograms/kg) of IL-1 alpha or IL-1 beta produced a biphasic fever in rabbits, but monophasic fever in rats. Febrile responses in rabbits induced by I.V. injection of IL-1 alpha or IL-1 beta were significantly greater than those in rats induced by these same injections. Furthermore, in both species, the pyrogenicity of I.V. IL-1 beta was greater than that of IL-1 alpha. 3. The intracerebroventricular injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.2-20 ng. In rabbits and rats, the ventricular injections of IL-1 alpha and IL-1 beta produced fever with almost the same pattern--monophasic, regardless of injection doses. Although febrile responsiveness of rabbits to ventricular injection of IL-1 alpha was greater than that of rats, responsiveness to IL-1 beta was almost the same in both species. Pyrogenicity of ventricular IL-1 beta was greater than that of IL-1 alpha. However, febrile responses in rats induced by ventricular injections of several doses (2-2000 ng) of prostaglandin E2 were greater than those in rabbits. 4. The present results show that febrile responsiveness of rabbits to I.V. IL-1 is significantly greater than that of rats. However, fever sensitivity within the central nervous system (CNS) of rats is not lower compared with that of rabbits. Therefore, we considered that between the two species there exist structural differences in the organum vasculosum laminae terminalis (OVLT), which is currently believed to be the pathway of pyrogen to the CNS and/or the site of production of pyrogenic prostaglandins. 5. Histological examinations showed that the rabbit's OVLT has two vascular components with capillaries, one in the layer near the third ventricle and the other in the layer near the subarachnoideal space. However, the rat's OVLT only has a single component, in the layer near the subarachnoideal space.(ABSTRACT TRUNCATED AT 400 WORDS)