Localized cutaneous blanching of preterm neonates following the topical application of a 10% solution of Neo-Synephrine attests to the permeability of immature skin. Skin permeability was evaluated in 18 healthy infants between 30 to 40 weeks of gestational age. The response consisted of speckles or islands of blanching which gradually coalesced to form a homogeneous pale area. Infants 30–35 weeks had a very rapid response which persisted from 30 minutes to 8 hours. A response was no longer apparent by 21 days of postnatal life. Infants 36–37 weeks had a longer lag period and responded less intensively. Infants 38–42 weeks failed to exhibit blanching in most cases. The degree of permeability correlated inversely with gestational age. Surface temperatures on strongly blanched and contiguous unblanched skin were identical when measured simultaneously. Toxicologic implications are clear. Other considerations include the intrauterine role of fetal skin as a dialyzing membrane, the relationship of skin structure to barrier function and the potential of further pharmacologic studies on the accessible cutaneous circulation.