The newborn infant's skin is not a complete barrier to the absorption of externally applied agents, particularly if it is damaged, diseased, or immature. Immaturity is the most important factor that determines percutaneous absorption. Very immature infants in the early neonatal period have a poorly developed epidermis, which is readily permeable to drugs. The main consequences of percutaneous absorption are hazardous. Topically applied agents are absorbed, causing toxic systemic effects that may result in illness and even death without the cause being recognized. No drug or antiseptic agent should be applied to the premature infant's skin without consideration of the effects that might result from percutaneous absorption. On a more optimistic note, the relatively permeable skin could be an advantage to the preterm infant by providing an alternative method of drug administration. The drug theophylline for example can be absorbed and produce therapeutic blood levels for up to 3 days after a single topical application. There is a need for the development of transdermal drug delivery systems for the newborn infant similar to those currently used for therapy in adults.