The effects of the bacterial endotoxin lipopolysaccharide (LPS) and interleukin (IL)-1beta on corticosterone secretion has been studied in vivo by employing the technique of in situ perfusion of the isolated rat left adrenal gland. Both LPS and IL-1beta dose-dependently raised corticosterone output, the response peaking at 60 and 90 min, respectively. IL-1 receptor antagonist dose-dependently reversed the effect of LPS and IL-1beta. The IL-1beta converting enzyme (ICE) inhibitor Ac-YVAD-CMK annulled the adrenal response to LPS, but did not affect that to IL-1beta. Collectively, these findings provide evidence that LPS, by enhancing adrenal production of IL-1beta, is able to evoke a sizable glucocorticoid response in the rat, thereby suggesting that local immuno-endocrine interactions may be operative in the adrenal gland of this species.