Increases in the maternal–fetal pH gradient that may occur during labor and delivery may increase the fetal concentration of local anesthetics. The authors evaluated effects pH changes on the transplacental concentration equilibrium of bupivacaine. They increased the maternal–fetal pH gradient in each of six pregnant ewes from a control value of 0.15 to 0.54 by hyperventilating the lungs of the ewe and infusing lactic acid into her fetus. After infusion of bupivacaine, 0.15 mg/kg, intravenously into the mother, the drug rapidly appeared in fetal blood, with values significantly increased over control values at 1 and 5 min. The fetal/maternal (f/m) ratios were increased significantly at 5, 15, and 30 min. The f/m ratios had stabilized by 15 min in both control and experimental states, suggesting that equilibrium had been achieved. The consistently low f/m ratios are explained by the presumed similarity of the ovine maternal and fetal protein binding rates to those of man. It is concluded that the maternal and fetal pH values are major factors in the determination of the f/m ratios.