There is evidence suggesting the involvement of the surfactant system in the development of lung diseases in cigarette smokers. The aim of the present study was to evaluate the effect of Ambroxol on lung epithelial permeability (LEP) in healthy smokers. Ambroxol is known to stimulate surfactant production. Twenty male patients aged between 20 and 60 years participated in the study. They all smoked at least 15 cigarettes daily for 10 years. We carried out a random double-blind study versus placebo: the drug (Ambroxol 75 mg) or the placebo were given once a day after breakfast for 30 days. Lung permeability was evaluated through scanning pulmonary scintigraphy by inhalation of the polydispersed liquid aerosol diethylenetriaminepentaacetic acid (DTPA), labelled with 99Tc, and delivered by a 'Venticis' system. LEP was expressed as the half-time clearance from the lung of 99Tc-DTPA (T50). The significance of the differences between the two treatments was determined by the Student's test for unpaired data. LEP was not different from the baseline value (T50 = 18.49 min) after placebo administration (T50 = 19.57 min). The patients receiving Ambroxol showed an increased LEP mean value (T50 = 18.36 min) in comparison with the baseline mean value (T50 = 16.41 min). Our results demonstrate that the treatment with Ambroxol was able to decrease LEP in 6 subjects, though not significantly.