We have previously reported that Escherichia coli bacteremia induces hypoperfusion and vasoconstriction of the rat small intestinal microcirculation. However, the mechanisms which mediate these responses are not clearly defined. Because serum levels of endothelins, a family of potent vasoconstrictor peptides, are increased during bacteremia, we postulated that endothelins contribute to intestinal hypoperfusion during infection. Using intravital microscopy, we characterized the effects of topically applied recombinant endothelin-1 on small intestinal arteriolar diameters and blood flow. Dose-dependent vasoconstriction of both large (A1) and small (A3) arterioles and hypoperfusion were observed. To assess whether endothelins contribute to alterations of the intestinal microcirculation during bacteremia, antiserum was used to inhibit endothelins during E. coli bacteremia. Endothelin inhibition resulted in restoration of blood flow and attenuation of vasoconstriction. Our results suggest that endothelins contribute to intestinal hypoperfusion and arteriolar vasoconstriction during bacteremia.