Effects of recombinant human interleukin-1 (IL-1) on electrical properties and unidirectional fluxes of Na+ and Cl- in rabbit ileum were examined in vitro employing the Ussing chamber technique. Serosal but not mucosal addition of Il-1 increased short-circuit current (Isc) in a concentration-dependent manner with a maximal effect occurring at 5 ng/ml and a half-maximal effect at 0.9 ng/ml. The time required for a maximal effect was between 30 and 40 min. Flux measurements revealed that serosal IL-1 reduced Na+ and Cl- absorption. The increase in Isc elicited by IL-1 was not altered by pretreatment of tissues with serosal atropine, tetrodotoxin, the H1-histamine receptor antagonist, mepyramine or removal of Ca2+ from the serosal bathing solution. The effects of IL-1 were inhibited by removal of Cl- from the bathing solutions, or by indomethacin or piroxicam. Levels of immunoreactive thromboxane B2 and 6-keto-PGF1 alpha and PGE2 were not significantly altered by IL-1. These results demonstrate that IL-1 can inhibit Na+ and Cl- absorption in rabbit ileum.