Chronic hepatitis C virus (HCV) infection has been recently identified as an aetiological agent in idiopathic pulmonary fibrosis. The present study was designed to determine the pulmonary clearance rate of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) in asymptomatic HCV antibody positive (HCV Ab+) patients and the role of 99mTc-DTPA aerosol scintigraphy in the early detection of lung involvement. Twenty-six non-smoker HCV Ab+ and HCV-RNA (+) patients (20 female, six male; aged 43±11 years), with no clinical pulmonary symptoms, and normal radiological findings, were studied. Thirty-one healthy non-smoker volunteers (24 female, seven male; aged 40±10 years) were taken as a control group. 99mTc-DTPA aerosol inhalation scintigraphy and pulmonary function tests were performed in all patients and in controls. On the basis of the scintigrams the percentage decline in activity per minute (Kep) was evaluated, which represented an accurate parameter of lung membrane permeability. The mean Kep values of healthy controls (0.78±0.13 for left lung, 0.79±0.14 for right lung) were significantly lower than HCV Ab+ patients (1.10±0.31 for left lung, 1.11±0.34 for right lung, P<0.001). But no significant change was observed in PFT (P>0.05). We conclude that subclinical alveolitis and/or interstitial lung disease may be present in patients with HCV Ab+, since it is known that an increase in the epithelial permeability of the lung is an early manifestation of interstitial disease. © 2002 Lippincott Williams & Wilkins, Inc.