Barker, Pierre M., and Richard E. Olver. Invited Review: Clearance of lung liquid during the perinatal period. J Appl Physiol 93: 1542-1548, 2002; 10.1152/japplphysiol.00092.2002.-At birth, the distal lung epithelium undergoes a profound phenotypic switch from secretion to absorption in the course of adaptation to air breathing. In this review, we describe the developmental regulation of key membrane transport proteins and the way in which epinephrine, oxygen, glucocorticoids, and thyroid hormones interact to bring about this crucial change in function. Evidence from molecular, transgenic, cell culture, and whole lung studies is presented, and the clinical consequences of the failure of the physiological mechanisms that underlie perinatal lung liquid absorption are discussed. lung liquid; sodium absorption; chloride secretion; epithelial sodium channel; cystic fibrosis transmembrane conductance regulator THE MECHANISMS RESPONSIBLE for lung liquid clearance during the neonatal period develop gradually during the latter part of the third trimester of pregnancy, but the phenotypic switch of the lung epithelium from net secretion to net absorption, triggered by events at birth, is sudden. Although lung liquid absorption at birth is "a performance without rehearsal," the lung may be called on for an encore in later life when these same mechanisms are activated to clear accumulated edema liquid.Many of the early studies of perinatal lung liquid clearance, which were mostly undertaken on the intact lungs of rabbits and sheep in the 1970s and 1980s, provided information in vivo on the time course and regulation of lung liquid clearance in a fully integrated physiological context. These data have been supported and augmented in the past decade by cloning of genes that regulate transepithelial ion transport [particularly the sodium pump (Na ϩ -K ϩ -ATPase) and the epithelial Na ϩ channel (ENaC)] and the use of molecular approaches that have uncovered information at a subcellular level.