Smoking is the major risk factor for the development of Chronic Obstructive Pulmonary Disease (COPD), but epidemiological data suggest that other etiological factors may also be involved. Chlamydia pneumoniae (Cpn) is an established cause of acute and chronic upper and lower respiratory tract infections. Data obtained from in vitro and in vivo studies indicate that Cpn infection can be involved in the development of both small airways disease and emphysema, the two major components of COPD. The aim of this study was to investigate the possible association between chronic Cpn infection and COPD. The study population was comprised of 199 consecutive patients who underwent bronchoscopy due to longstanding airway symptoms and for whom spirometry and serum samples for serology were available. Acute and convalescent sera were analysed for specific IgG and IgA Cpn antibodies using microimmunofluorescence. Chronic Cpn infection, defined as persistent elevated titres of IgA > or = 1/64, was present in 85 patients. Chronic infection was associated with smoking and higher age, but no gender difference was observed. Thirty patients had COPD, defined as FEV1/FVC < 70% without any features of asthma. Patients with COPD were older than those without, and there was no association with gender in this group. A statistically significant association, remaining after correction for smoking, was observed between chronic Cpn infection and COPD, and there was a trend for decreasing lung function with increasing antibody titres. The results suggest that chronic Cpn infection may be an independent risk factor for the development of COPD.