The application of99mTc-DTPA radioaerosols to a variety of clinical disorders is described. With the development of simple equipment that can deliver very small droplets, this approach has become increasingly popular for measurements of the distribution of ventilation in patients with obstructive lung disease and suspected pulmonary embolism. In addition. by determining the rate at which the radionuclide is cleared from the lung, information has been obtained concerning the permeability of the pulmonary epithelium to extracellular indicators. Accelerated clearance rates have been found in patients with a variety of chronic interstitial lung diseases indicating that epithelial permeability is increased. Accelerated clearance rates have also been found with acute inflammation of the lung such as the adult respiratory distress syndrome and pneumocystis pneumonia. Furthermore, rapidly reversible increases in99mTc-DTPA clearance occur in smokers and may be related to the inflammatory changes that contribute to the development of emphysema.