Lactoferrin and lysozyme are proteins found in high concentrations on mucosal surfaces, and they have activities potentially important for the modulation of inflammation. To investigate whether these proteins might contribute to the modulation of the intraluminal airway inflammation associated with chronic bronchitis, lactoferrin and lysozyme were measured in bronchoalveolar lavage (BAL) fluid from 22 subjects with chronic bronchitis and, for comparison, with 10 symptom-free smokers and 16 normal subjects. As a further control, transferrin, a protein structurally homologous to lactoferrin but not known to arise in airway epithelial cells, was also measured. BAL was performed by sequentially instilling and retrieving five 20 ml aliquots of normal saline solution into each of three sites. Analyzing the first aliquots separately from the later four provided fluid that was enriched for airway contents. The concentration of lactoferrin (11.83 +/- 2.86 micrograms/ml vs 0.68 +/- 0.18 micrograms/ml, p less than 0.00001), and lysozyme (6.75 +/- 1.51 micrograms/ml vs 0.52 +/- 0.09 microgram/ml, p less than 0.00001), but not transferrin (3.22 +/- 0.38 microgram/ml vs 2.68 +/- 0.24 micrograms/ml, p = 0.55) was higher in the bronchial sample lavage fluid, suggesting an airway origin for lactoferrin and lysozyme. In subjects with chronic bronchitis, bronchial sample lactoferrin (23.1 +/- 0.5 micrograms/ml) and lysozyme (12.6 +/- 3.5 micrograms/ml) were elevated compared with the normal subjects' lactoferrin (1.9 +/- 0.5 micrograms/ml, p less than 0.0001) and lysozyme (0.77 +/- 0.22 microgram/ml, p less than 0.0001) and the symptom-free smokers' lactoferrin (4.1 +/- 0.8 micrograms/ml, p = 0.005) and lysozyme (4.9 +/- 1.3 micrograms/ml, p = 0.02). Transferrin concentrations did not demonstrate the same relationships. Finally, when the content of bronchial sample lactoferrin and lysozyme were compared with the content of bronchial sample neutrophils, poor correlations were found, which may imply an airway epithelial origin for the two proteins. Thus lactoferrin and lysozyme appear to arise in the lower respiratory tract within the airways and their levels are elevated in association with chronic bronchitis. This suggests that lactoferrin and lysozyme may contribute to the modulation of airway inflammation in chronic bronchitis.