A severe hypoxic insult is known to induce dramatic reductions in newborn intestinal blood flow and is, thus, considered a vector for the development of neonatal intestinal ischemic diseases. Dopexamine (DPX) is a novel synthetic agent that has potent B2-adrenoceptor and dopaminergic activity, the clinical effects of which include an increase in cardiac output and in mesenteric blood flow. Having previously shown that infusion of DPX before hypoxia (HYP) mitigated the reduction in newborn mesenteric blood flow, we sought to define its efficacy when given after an established hypoxic insult. Ultrasonic transit time blood flow probes were placed around the ascending aorta and cranial mesenteric artery of anesthetized, mechanically ventilated 0 to 2-day-old piglets. Small bowel mucosal oxygenation was observed with a tissue oxygen monitoring system. After stabilization, animals were subjected to one of the following: HYP (FIO2 = 0.12) for 60 minutes (n = 12); DPX (5 microg/kg/min) infusion begun 10 minutes after induction of HYP/DPX (n = 11). Almost no alterations in any of the monitored variables were shown in a group (n = 5) of similarly instrumented, untreated animals. In contrast, although both hypoxic piglet groups experienced significant (P < 0.05, analysis of variance) declines from baseline cardiac output, mesenteric blood flow, and mucosal oxygenation, each of these deleterious effects was significantly (P < 0.05) blunted in the DPX-treated animals. During periods of systemic hypoxemia, the reductions in neonatal mesenteric blood flow and oxygenation can be somewhat blunted by DPX. As such, this agent may prove of clinical benefit when an infant is threatened by a hypoxic episode.