Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB-HI, n = 10) and in patients with obstructive chronic bronchitis (COPD-HI, n = 10) by analyses of the sol phase of spontaneously expectorated sputum (SSP). As compared with the CB-HI group, the COPD-HI group had significantly higher (p < 0.05) levels of myeloperoxidase (MPO) and tumor necrosis factor (TNF)-alpha in their SSP, whereas the degree of plasma protein leakage (SSP-to-serum ratio of plasma proteins) and the levels of interleukin (IL)-8, secretory IgA, and lactoferrin were similar in the two groups. These findings point to differences in pathophysiology in CB-HI and COPD-HI. The high level of TNF-alpha in the SSP of COPD-HI patients is in accord with the proposed role of TNF-alpha in the development of airway obstruction in COPD patients. In apparent contradiction, low levels of TNF-alpha were found in the SSP of noninfected but otherwise similar COPD patients (n = 9). This finding, however, does not exclude an exaggerated TNF-alpha response to infection or another stimulus in the airways of COPD patients. The SSP levels of MPO and IL-8, and the degree of plasma protein leakage in the COPD-HI group, were retrospectively compared with and found significantly higher than those of noninfected COPD patients, suggesting a more marked inflammatory response in COPD-HI. Whether this reflects a direct cause-and-effect relationship should be addressed in a future long-term prospective study involving repeated measurements in the same patients.