Interleukin-1 beta (IL-1 beta) production in the brain and the spleen was investigated in rabbits which show febrile tolerance to bacterial endotoxin, lipopolysaccharide (LPS). Febrile tolerance to LPS was induced by daily intravenous (i.v.) injections of LPS (4 micrograms/kg, i.v.) for 5 days. In the LPS-tolerant rabbits, the second phase of the biphasic fever induced by i.v. injection of LPS (4 micrograms/kg) disappeared, although the first phase remained intact. In situ hybridization and immunohistochemical studies revealed that IL-1 beta production was observed in the circumventricular organs, such as the organum vasculosum laminae terminalis (OVLT), subfornical organ (SFO) and area posterema (AP), 1 h after the first exposure to i.v. injection of LPS (4 micrograms/kg) (acute rabbits). In contrast, IL-1 beta production in these circumventricular organs disappeared in the LPS-tolerant rabbits. IL-1 beta production was observed in the spleens of the acute and the LPS-tolerant rabbits after i.v. injections of LPS. The cells which produced IL-1 beta in the spleen following LPS injections were confirmed to be monocytes/macrophages and polymorphonuclear leukocytes by immunohistochemistry in both the acute and the LPS-tolerant rabbits. The LPS-injected acute rabbits showed a significant increase in the number of IL-1 beta-immunoreactive monocytes/macrophages, compared with that in the saline-injected acute rabbits. However, there was no significant difference in immunoreactive cell numbers between the saline-injected acute and LPS-injected tolerant rabbits, or between the LPS-injected acute and the LPS-injected tolerant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)