Our previous studies have demonstrated that bacteremia induces vasoconstriction and hypoperfusion of the small intestinal microcirculation. The present study used time-transit doppler flowmetry, intravital microscopy, and laser doppler fluximetry to measure superior mesenteric artery (SMA) blood flow, intestinal microvascular blood flow, and mucosal perfusion. The aim of this study was to determine the relative importance of the intestinal macro- and microcirculations in the development of mucosal hypoperfusion. Animals were infused with 5 x 10(8) colony-forming units of Escherichia coli/100 g body weight or saline as control. Bacteremia induced a normotensive, normodynamic state. SMA blood flow was unaffected by bacteremia, but arteriolar vasoconstriction (approximately -30%) and microvascular hypoperfusion (approximately -70%) occurred. Mucosal perfusion decreased by 40% from baseline, and was temporally correlated with microvascular hypoperfusion. From these data, we conclude that the microcirculation has a central role in the development of mucosal hypoperfusion during bacteremia.