To determine whether there are changes in blood gas and acid-base status with advancing gestation in the fetal lamb, similar to that reported in the human fetus, blood gas, acid-base, and blood metabolite values were measured in 447 control, arterial blood samples from 108 chronically instrumented fetal lambs between 103 and 146 days gestation. With advancing gestation, Po(2), pH, O(2) saturation, and O(2) content fell significantly, while Pco(2) and hemoglobin concentration increased. Blood glucose and lactate concentrations were unchanged, although the lactate level increased with decreasing Po(2), particularly when below ~13 mmHg. Multiple linear regression indicated that increasing fetal number was associated with decreased Po(2) and glucose level and increased pH, HCO(3)(-), base excess, and lactate concentration. Hemoglobin concentration was higher in female than male lambs. Overall, there was a linear relationship between glucose concentration and birth weight. It is concluded that in fetal lambs as in the human fetus, there are changes in blood gas and acid-base status with advancing gestation. This may be due to the decrease in fetal weight-normalized uterine and umbilical blood flows than occurs in these and other species as gestation proceeds. In addition, the reduced birth weight in twin and triplet lambs may be due to hypoglycemia rather than hypoxemia.