The influence of lipopolysaccharide (LPS) and the endogenous pyrogens, recombinant human interleukin 1 (rHu-IL 1) and tumor necrosis factor (rHu-TNF), on acute inflammation was investigated in rats. LPS (0.3-3 micrograms/kg i.v.), rHu-IL 1 alpha (3-30 micrograms/kg), rHu-IL 1 beta (0.3-3 micrograms/kg) and rHu-TNF (3-30 micrograms/kg) inhibited the hind paw edema induced by carrageenan in a dose-related manner. The potency of rHu-IL 1 beta was 10 times or more than of rHu-IL 1 alpha. rHu-IL 1 alpha and rHu-TNF also inhibited the dextran-induced hind paw edema. Both types of rHu-IL 1 (0.001-10 ng/paw) neither inhibited nor enhanced the edema when given directly into the inflamed paw. rHu-IL 1 alpha did not show any significant anti-edema activity in adrenalectomized rats. The 3 cytokines tested caused a significant increase in the plasma levels of ACTH and corticosterone after i.v. administration; the potency of rHu-IL 1 beta was about 10 times that of rHu-IL 1 alpha. These results suggest that both rHu-IL 1 and rHu-TNF inhibit paw edema at least in part through pituitary-adrenal axis stimulation, and that rHu-IL 1 has no pro-inflammatory action in the paw edema induced by carrageenan in rats.