We tested the hypothesis that endotoxin increases the heterogeneity of gut capillary transit times and impairs oxygen extraction. The gut critical oxygen extraction ratio was determined by measuring multiple oxygen delivery-consumption points during progressive phlebotomy in eight control and eight endotoxin-infused anesthetized pigs. In multiple 1- to 2-g samples of small bowel, we measured blood volume (radiolabeled red blood cells) and flow (radiolabeled 15-microns microspheres) before and after critical oxygen extraction. Red blood cell transit time (= volume/flow) multiplied by morphologically determined capillary/total blood volume gave capillary transit time. During hemorrhage, capillary/total blood volume did not change in the endotoxin group (0.5 +/- 4.5%) but increased in the control group (17.6 +/- 2.5%; P < 0.05) due to a decrease in total gut blood volume. Flow decreased significantly in the endotoxin group (36 +/- 10%; P < 0.05) but not in the control group (12 +/- 10%). Capillary transit-time heterogeneity increased in the endotoxin group (12.3 +/- 4.9%) compared with the control group (-5.8 +/- 7.4%; P < 0.05), predicting a critical oxygen extraction ratio 0.14 lower in the endotoxin group than in the control group (K. R. Walley. J. Appl. Physiol. 81: 885-894, 1996). This matches the measured difference (endotoxin group, 0.60 +/- 0.04; control group, 0.74 +/- 0.03; P < 0.05). Increased heterogeneity of capillary transit times may be an important cause of impaired oxygen extraction.