During the last half of pregnancy, the fetal guinea pig grows exponentially at 7.1%/day. In order to define the metabolic requirements of the gravid uterus during this period of rapid growth, catheters were placed in the femoral artery and uterine vein of guinea pigs at gestational ages ranging from 40 days to term (68 days). The animals were studied in the unstressed state after full recovery from surgery and anesthesia. Arterial and venous concentrations of oxygen, glucose, lactate, acetoacetate, beta-hydroxybutyrate, and acetate were measured, and metabolic quotients and coefficients of extraction were calculated. The glucose/oxygen quotient did not change significantly in the last half of pregnancy averaging 1.26, while the lactate/oxygen quotient remained unchanged at -0.42, and the (glucose + lactate)/oxygen quotient remained unchanged at 0.82. Coefficients of extraction of glucose and oxygen increased linearly with gestational age. The increase in supply of substrates for the rapid growth of the conceptus toward the end of gestation is accounted for by increasing extraction of substrate and by greatly increasing blood flow with increasing gestation. While glucose remains the major metabolic fuel of the guinea pig conceptus and acetate is consistently taken up by the uterus, these substrates alone cannot account for the metabolic fate of the oxygen taken up and fall far short of the predicted nutritional requirements of the fetus for both oxidative metabolism and growth.