Angiotensin II (ANG II) has been shown to have proinflammatory properties. To investigate whether ANG II is involved in the lipopolysaccharide (LPS)-induced production of a pyrogenic/proinflammatory cytokine, interleukin-6 (IL-6), we examined the effects of an angiotensin-converting-enzyme (ACE) inhibitor, lisinopril, on LPS-induced fever and on the expression of IL-6 mRNA in the spleen of dehydrated rats (in which the secretion of ANG II increases). The results showed that the ACE inhibitor significantly inhibited LPS-induced fever as well as the splenic expression of IL-6 mRNA in dehydrated rats. It is suggested that endogenous ANG II may be involved in the production of IL-6 that occurs in response to LPS, and thereby contribute to the LPS-induced febrile response in dehydrated rats