The aim of this prospective observational study was to determine those factors influencing bacterial colonization in patients with stable chronic obstructive pulmonary disease (COPD). Eighty-eight outpatients with stable COPD and 20 patients with normal spirometry and chest radiography (controls) had a fibreoptic bronchoscopy performed with topical aerosol anaesthesia. Bacterial colonization was determined using the protected specimen brush (PSB) with a cut-off > or = 10(3) colony-forming units (CFU x mL(-1)). The influence of age, degree of airflow obstruction, smoking habit, pack-yrs of smoking, and chest radiographic findings on bacterial colonization were assessed by univariate and multivariate analysis. Significant bacterial growth was found in 40% of patients and in none of the controls. Haemophilus influenzae, Streptococcus viridans, S. pneumoniae and Moraxella catarrhalis were the most frequent pathogens. After adjustment for other variables, severe airflow limitation (odds ratio (OR) 5.11, 95% confidence interval (CI) 1.45-17.9) and current smoking (OR 3.17, 95% CI 2.5-8) remained associated with positive bacterial cultures. When only potentially pathogenic micro-organisms were considered, significant bacterial growth was found in 30.7% of patients, with severe airflow obstruction (OR 9.28, 95% CI 2.19-39.3) being the only variable independently associated with positive bacterial cultures. Our results show that stable chronic obstructive pulmonary disease patients have a high prevalence of bacterial colonization of distal airways which is mainly related to the degree of airflow obstruction and cigarette smoking.