The purpose of the present study was to compare the effects of two mucolytic drugs with different mechanism of action on mucociliary transport (MCT). N-acetylcysteine (NAC-600 mg/day) and ambroxol (AMB-90 mg/day) were administered according to a double-blind cross-over scheme to 12 heavy smokers suffering from hypersecretory bronchitis and homogeneous reduction of the MCT. Placebo of both treatments was administered during an interval of ten days between the administrations of NAC and AMB. The entire treatment period was 30 days. The data were analyzed according to ANOVA for the two-period cross-over clinical trial. The results indicate that: NAC and AMB, administered both before and after placebo, produce a significant increase in MCT, NAC showed a slightly greater efficacy than AMB, but the differences are not statistically significant. The overall efficacy of NAC and AMB is consistently greater than that of placebo. The sequence of administration of the drugs does not influence their effect.