99mTc-DTPA is a low molecular weight substance which is believed to pass through the pulmonary epithelium when it is inhaled as an aerosol. We performed 99mTc-DTPA inhalation studies in 10 nonsmoking normal subjects and 10 patients with biopsy proven idiopathic interstitial pneumonia prior to therapy. 99mTc-DTPA aerosol was inhaled for 3 min with the subject in the supine position and radioactivity was measured anteriorly with a gamma camera and recorded on a computer. Measurements were performed for 3 min with the subject inhaling aerosol and for the subsequent 30 min with the subject in the same position. Time activity curves from the five regions of interest (ROIs) including the entire left lung, the entire right lung, and the upper, middle and lower third of the right lung were separately fitted to a single exponential function for the initial 7 min following cessation of inhalation, and the respective clearance half life (t1/2) in min was calculated. Lung function data, arterial blood gas tensions and blood chemistry were also obtained for comparison with the t1/2 values. The t1/2 values were significantly smaller in all ROIs in patients with idiopathic interstitial pneumonia than in normal subjects, indicating a increased pulmonary epithelial permeability in these patients. There was no relationship between t1/2 and %DLco, %DLco/VA, PaO2, or LDH. Although the true pathophysiologic significance of t1/2 measured using 99mTc-DTPA aerosol is still not known, we consider that this measurement may be an important indicator of nonrespiratory lung function, in particular the degree of alveolar epithelial damage.