A potential role of surfactant in COPD pathogenesis is not yet clearly demonstrated. Cigarette smoke is an important risk factor for COPD and it is known to adversely affect surfactant. In a series of 20 smoker, non-asthmatic COPD patients compared with 5 nonsmoker healthy controls we found a marked decrease (about 6-7 times) of total phospholipids in bronchoalveolar lavage fluids. We were not able to find differences in % composition, with the exception of phosphatidylglycerol-cardiolipin, which appeared significantly increased in smoker COPD patients (p < 0.02). An alteration of mucociliary clearance and an impairment of antimicrobial defence might be important surfactant related factors in COPD, but no definitive data are available. We do not know at present if a therapy increasing surfactant would be of any value in COPD treatment. Surfactant replacement therapy is at present advisable only for those conditions in which a surfactant impairment plays (IRDS) or seems to play (ARDS) a crucial role. Pharmacologic stimulation of type 2 pneumocytes could have several advantages over replacement therapy. Ambroxol is probably one of the most promising surfactant stimulating agents, but preliminary data show that in smoker COPD patients drug dosages higher than those usually employed to affect bronchial mucus are necessary to obtain a significant increase of surfactant phospholipids.