Local anesthetics are weakly basic drugs that are principally bound to 1-acid glycoprotein. Placental transfer depends on three factors: (1) pKa, (2) maternal and fetal pH, and (3) degree of protein binding. Except for chloroprocaine, fetal acidosis produces higher fetal-to-maternal drug ratios because binding of hydrogen ions to the nonionized form causes trapping of the local anesthetic in the fetal circulation. Highly protein-bound agents diffuse poorly across the placenta; thus, greater protein binding of bupivacaine and ropivacaine, compared with that of lidocaine, likely accounts for their lower fetal blood levels. Chloroprocaine has the least placental transfer because it is rapidly broken down by plasma cholinesterase in the maternal circulation.