The growth of uterine oxygen and glucose uptakes (Qo2, Q glucose) throughout pregnancy was determined in sheep with chronically implanted uterine artery electromagnetic flow probes and arterial and uterine venous catheters. The flow probe measurements were corrected to total uterine blood flow by means of an equation based on simultaneous flow probe and radioactive microsphere determinations. Uterine Qo2, and Q glucose increased logarithmically as gestation progressed. During the last third of gestation, the mean Qo2 for twin pregnancies was 44% higher than Qo2 for single pregnancies. In the last 3 weeks of gestation the uterine glucose/oxygen quotient was 0.76 (95% confidence limits 0.65–0.87), which is significantly less than one and significantly greater than the 0.46 umbilical glucose/oxygen quotient determined in previous studies. This result indicates that substrates other than glucose are used in large amounts in order to satisfy the requirements of uterine oxidative metabolism in late pregnancy and that the placenta has a relatively high glucose/oxygen quotient. Uterine arteriovenous differences of fructose and pyruvate measured at intervals throughout gestation revealed that there is no significant uptake of these substrates by the pregnant uterus.