The aim of this study is to investigate the effect of one-course chemotherapy on the pulmonary epithelial permeability. Eighteen patients (18 male; mean age: 59+/-10 years) with lung cancer (11 non-small cell, 7 small cell) inhaled 40 mCi (1,480 MBq) (99m)Tc-diethylenetriaminepentaacetic acid (DTPA). Thirty images of 1-min duration were acquired from posterior projection. The first 7 min of the decay-corrected time activity curves were used to calculate lung clearance half-time. Clearance half-times of (99m)Tc-DTPA from the peripheral regions of the lungs were 42+/-19 min before and 56+/-34 min after chemotherapy (p=0.009); from the central regions, clearance half-times were 112+/-94 min before and 160+/-125 min after chemotherapy (p=0.005). This decrease in clearance rate might be related to decreasing mucociliary clearance rate due to the toxic effect of the chemotherapy regimen on cilia movement and/or mucus structure. (99m)Tc-DTPA radioaerosol study can be used to monitor the toxic effects of chemotherapy on the pulmonary epithelium and possibly on mucociliary function.