This study was designed to determine the effects of severe hypoxemia on newborn piglet visceral blood flow. While the hemodynamic effects of a severe hypoxemic insult are well characterized in newborn animals, its impact on organ perfusion in premature infants is not well characterized. Cannulas were placed in the femoral vessels and left atrium of term (1-14 days old) and prematurely delivered (cesarean section at 90% of term gestation) piglets. After stabilization, some animals were subjected to 1 h of ventilator-controlled hypoxia (yielding PaO2 approximately = 30-40 torr) followed by 30 min of reoxygenation; the remaining animals served as unchallenged controls. Radiolabeled microspheres were injected in all animals at times 0 min (baseline), 5 and 60 min (hypoxia), and 90 min (reoxygenation). Blood flows (mL/min/g tissue) to organs were determined using reference organ techniques. Control animals displayed no alterations in any of the variables monitored. Throughout the experimental period, organ blood flows were almost uniformly lower (p<.05, ANOVA) in premature versus term animals. The trend toward increased cerebral and cardiac blood flows during hypoxia observed in the premature piglets was similar to that of term animals, but of lower magnitude. In term piglets, hypoxia produced an immediate and significant (*p<.05) decline in small-intestinal blood flow followed by autoregulatory escape (2.02+/-0.17 mL/min/g at time 0, 1.56+/-0.15 mL/min/g at 5 min hypoxia, 1.88+/-0.18 mL/min/g at 60 min hypoxia, 2.26+/-0.19 mL/min/g at 30 min reoxygenation), an effect not readily observed in the premature piglets (0.48+/-0.10 mL/min/g at time 0, 0.44+/-0.07 mL/min/g at 5 min hypoxia, 0.46+/-0.10 mL/min/g at 60 min hypoxia, 0.42+/-0.08 mL/min/g at 30 min reoxygenation). However, mucosal blood flows measured in these younger animals declined throughout the experimental period to almost 50% of baseline, compared to a complete restoration to baseline blood flow observed following reoxygenation of term piglets. Intestinal blood flow in premature infants is small when compared to term animals, and alterations in small intestinal blood mucosal flow induced by hypoxia appear less well tolerated by the premature animals. Taken together, this may in part account for the increased risk of developing intestinal ischemic diseases in premature infants who are even temporarily exposed to a severe hypoxic challenge.