N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) is lipophilic substance and permeates through the alveolar epithelium via intracellular transport, whereas 99mTc-DTPA is water-soluble substance and permeates through the alveolar epithelium via paracellular transport. We performed inhalation lung imaging using 123I-IMP and 99mTc-DTPA in order to assess alveolar epithelial permeability in 4 patients with restrictive ventilatory impairment, and 5 volunteers including one smoker. The time-activity (T/A) curves of 123I-IMP were well fitted into two compartments, first and slow, by least-squares fit technique, in contrast to 99mTc-DTPA fitted well with one compartment. In 4 normal volunteers, the T/A curves of the lower pulmonary fields declined faster than those of other pulmonary fields. In 99mTc-DTPA studies, the Kep values of patients with restrictive ventilatory impairment (n = 4) were higher than those of normal volunteers (n = 4) (2.14 +/- 0.30 x 10(-4) vs 1.48 +/- 0.41 x 10(-4), p less than 0.005). On the other hand, in 123I-IMP studies, the Kep values of the patients were much lower than those of normal volunteers (6.79 +/- 0.55 x 10(-5) vs 1.52 +/- 0.45 x 10(-3), p less than 0.005).