Studies were carried out to determine the effects of IL-1 on newborn intestinal hemodynamics. IL-1 increased release of ET-1 by primary endothelial cells in a dose-dependent manner; as well, it reduced expression of the endothelin ET_B receptor on endothelial cells and increased expression of the ET_A receptor on vascular smooth muscle cells. IL-1 increased endothelial cell eNOS expression, but did not enhance eNOS activity as evidenced by release of NOx into conditioned medium in response to acetylcholine or shear stress. The effects of IL-1 on flow induced dilation were evaluated in terminal mesenteric arteries in vitro. Pretreatment with IL-1 (1 ng; 4 hr) significantly attenuated vasodilation in response to flow rates of 100 and 200 µl/min. This effect was mediated, in part, by the endothelin ET_A receptor; thus, selective blockade of ET_A receptors with BQ610 nearly restored flow induced dilation. In contrast, exogenous ET-1 only shifted the diameter - flow curve downward without altering % vasodilation in response to flow. The effects of IL-1 on ileal oxygenation were then studied using in vivo gut loops. Intra-mesenteric artery infusion of IL-1 upstream of the gut loop caused ileal vasoconstriction and reduced the arterio-venous O₂ difference across the gut loop; consequently, it reduced ileal oxy-genation by 60%. This effect was significantly attenuated by pretreatment with BQ610. These data support a linkage between the proinflammatory cytokine IL-1 and vascular dysfunction within the intestinal circulation, mediated, at least in part, by the endothelin system.