Ampicillin has been most thoroughly studied in regard to placental transfer. Both during the first/second trimester and at term, fetal drug levels rose slowly to reach values similar to those in the maternal circulation 1-3 h after maternal drug administration; thereafter, fetal drug levels exceeded corresponding maternal values. Amniotic fluid levels were low during early gestational periods; during late gestation these levels were significant and even exceeded corresponding maternal values 6-8 h after drug administration. Slow exchange rates and fetal micturation may be responsible for the elevated ampicillin levels during late gestation. Administration via the intramuscular (recommended with 0.5 g every 4-6 h) or intravenous routes, but not by the oral route, resulted in adequate drug levels. Because of increased plasma clearance of ampicillin during pregnancy, a dose increase in pregnant patients may be necessary to obtain adequate drug levels. Amoxillin and azidocillin have been suggested to give effective drug levels even after oral administration, except during labor. The fetal levels of epicillin and benzylpenicillin (Penicillin G) were lower than the corresponding maternal values; amniotic fluid concentrations of these two drugs were elevated during late, but very low during early gestation, similar to the situation with ampicillin. Methicillin and sulbenicillin were effectively transferred across the placenta (similar to ampicillin), while dicloxacillin was not. The low concentrations of dicloxacillin in the fetus and amniotic fluid may be the results of extensive protein binding (greater than 90%) of this drug in maternal blood. Other highly bound penicillins such as cloxacillin and flucloxacillin have not yet been investigated in regard to placental transfer. Excretion of penicillins in human milk was usually very limited. Following therapeutic doses, the mean milk concentrations were 0.1-0.6 microgram/ml for amoxicillin, 0.1-0.2 microgram/ml for epicillin, about 0.5 microgram/ml for sulbactam, 2-2.5 micrograms/ml for ticarcillin, and 0.1-0.4 microgram/ml for aztreonam.