The role of anti-neutrophil cytoplasmic autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) in chronic airway infections was investigated. The serum BPI-ANCA titer was correlated with the severity of clinical symptoms in patients with chronic airway infections (P < 0.01), and the serum BPI-ANCA titer decreased with the improvement of the clinical picture, compared with its deterioration (P < 0.05). The serum BPI-ANCA titer was significantly higher in patients with far-advanced lesions on chest X-rays than in patients with milder lesions (P < 0.01) and in patients with reduced respiratory function (P < 0.05). Also, the serum BPI-ANCA titer was significantly higher in patients with prolonged colonization of gram-negative bacteria than in those without prolonged gram-negative bacterial colonization (P < 0.05). When neutrophils from healthy volunteers were incubated with BPI-ANCA before stimulation with lipopolysaccharide (LPS), neutrophil elastase levels decreased in a dose-dependent manner (P < 0.01). The phagocytic activity of neutrophils was significantly inhibited by BPI-ANCA in a dose-dependent manner (P < 0.01). The above findings suggest that BPI-ANCA, an autoimmune factor, appears during the course of chronic airway infections, and that this autoimmune factor may make chronic airway infections more intractable, by inhibiting the phagocytic activity of neutrophils for gram-negative bacteria.