The kinetic disposition of ethanol was studied in neonatal lambs. The mean plasma clearance rate was 36 mg/l/h, 17% of that in near-term pregnant sheep. Activity increased slowly during the first 5 days of life. Hepatic alcohol dehydrogenase activity in the neonatal lamb was only 7% of that in adult sheep, but was similar to activity in the near-term fetus. Placental enzyme activity was even lower than that in the fetus and neonate, suggesting only a minor role for it in the metabolic disposition of ethanol during pregnancy. The pH optimum for alcohol dehydrogenase was higher in the fetus and neonate (9.6) than in maternal liver or placenta (9.0). The pharmacodynamic consequences of prolonged neonatal exposure to ethanol due to impaired metabolism remain to be explored.