The barrier properties of the skin were examined in 223 studies in 70 newborn infants of 25 to 41 weeks' gestation, aged from 1 hour to 26 days. Percutaneous drug absorption was studied by observing the blanching response to solutions of 1% and 10% phenylephrine applied to a small area of abdominal skin. Skin water loss was measured at the same site using an evaporimeter. Infants of 37 weeks' gestation or more showed little or no drug absorption and had low skin water losses, indicating that their skin is an effective barrier. By contrast, infants of 32 weeks' gestation or less showed marked drug absorption and high skin water losses in the early neonatal period, indicating that their skin is defective as a barrier. Both drug absorption and water loss in these infants fell steadily; by about 2 weeks of age the skin of the most immature infants functioned like that of mature infants. The varying barrier properties can be explained by the poor development of the stratum corneum in the more premature infants at birth and its rapid maturation after birth. The trauma caused to the skin by use of adhesive tape and the fixation of transcutaneous oxygen electrodes resulted in increased drug absorption and water loss from the damaged area.