Peripheral airspace epithelial permeability (PAEP) to diethylentriaminopentacetate (DTPA), an index of pulmonary integrity, was measured in 3 groups of subjects for different purposes: (1) to establish vertical regional reference values; (2) to determine the physiological role of acute doubling of total pulmonary blood flow; (3) to quantify the pulmonary epithelial damage in smokers and the possibility of lung protection by an agent stimulating surfactant production. This study broadens previous knowledge of PAEP. First of all, regional reference values are given for young normal nonsmoking subjects and the existence of a vertical gradient of PAEP is confirmed. Furthermore, this study shows that this gradient is independent of the vertical blood flow gradient, since an acute increase of total blood flow in pneumonectomized patients does not modify the regional distribution of PAEP. Finally, it is confirmed that the cigarette smoker's lung is more permeable than the controls and that probably a drug-stimulating surfactant production gives some protection against damage due to chronic smoking.