The early diagnosis of diffuse infiltrative lung disease (DILD) is important in prognosis and it is necessary to develop a noninvasive, inexpensive, and rapid diagnostic tool for suspected cases of DILD. Thus, we measured the epithelial permeability via radioisotope (99mTc-DTPA) in 22 patients with DILD for clinical application of the clearance rate (T1/2LB) of radioisotope on the early diagnosis of DILD. We divided the patients with DILD into the early and late stages according to the derangements of the diffusion capacity for carbon monoxide. The T1/2LB in patients with DILD were significantly shorter when compared with those with normal control in all lobes. However, 40 to 58 percent of T1/2LB in patients with DILD overlapped normal values (2 SDs of mean of T1/2LB of normal control) dependent on specific lung regions. The T1/2LB of patients with early-stage DILD was longer than that of patients with late-stage DILD in right upper and middle lobes. Although T1/2LB of 99mTc-DTPA, the index of alveolar epithelial permeability, was shortened in patients with DILD with normal diffusing capacity, it was difficult to detect early-stage DILD by measuring alveolar epithelial permeability because of many overlaps of T1/2LB between early-stage DILD and normal control.