Although recent studies have shown that gut absorptive function is significantly depressed even in the early hyperdynamic phase of sepsis, the mechanism responsible for this is unknown. Tumor necrosis factor (TNF-α) is a potent mediator of shock resulting in a marked inflammatory response leading to mucosal erosions of the gut and multiple organ failure. Although TNF is elevated in early sepsis, it remains unknown whether TNF plays any role in the depression of gut absorptive function under these conditions. To study this, we used the 1 hr D-xylose absorption test. C3H/HeN mice (n = 12) were lightly anesthetized, and a femoral artery and the portal vein were cannulated. After recovery from anesthesia, 125 μg recombinant murine TNF- α (rMuTNF-α) kg body weight was given via the tail vein to one group of animals, while another group received an equivalent volume of saline (sham). One hour later, D-xylose was given orally. The systemic blood pressure was recorded 1 hr thereafter and D-xylose concentration in a sample of portal blood was determined colorimetrically. Results show that, while the systemic pressure was elevated 2 hr after administration of rMuTNF-α, D-xylose absorption was severely depressed. Thus the depressed gut absorption function seen in the early stage of sepsis may be mediated directly or indirectly by TNF-α.