The metabolic adaptation of the hind limb in the fetus to a reversible period of adverse intrauterine conditions and, subsequently, to a further episode of acute hypoxemia has been examined. Sixteen sheep fetuses were chronically instrumented with vascular catheters and transit-time flow probes. In 9 of these fetuses umbilical blood flow was reversibly reduced by 30% from baseline for three days (UCC) while the remaining fetuses acted as sham-operated, age-matched controls. Acute hypoxemia was subsequently induced in all fetuses by reducing maternal F_iO₂ for 1 h. Paired hind limb arterio-venous blood samples were taken at appropriate intervals during cord-compression and acute hypoxemia and, using femoral blood flow and the Fick principle, substrate delivery, uptake and output were calculated. Umbilical cord compression reduced blood oxygen content and delivery to the hind limb and increased hind limb oxygen extraction and blood glucose and lactate concentration in the fetus. However, hind limb glucose and oxygen consumption were unaltered during umbilical cord compression. In contrast, hind limb oxygen delivery and uptake were significantly reduced in all fetuses during subsequent acute hypoxemia but glucose extraction, oxygen extraction and hind limb lactate output significantly increased in sham-control fetuses only. Pre-exposure of the fetus to a temporary period of adverse intrauterine conditions alters the metabolic response of the fetal hind limb to subsequent acute stress. Additional data suggest that circulating blood lactate may be derived from sources other than the fetal hind limb under these circumstances. The lack of hind limb lactate output during acute hypoxemia in UCC fetuses, despite a significant fall in oxygen delivery to and uptake by the hind limb, suggests that the fetal hind limb may not respire anaerobically following exposure to adverse intrauterine conditions.