Autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) were found in patients with cystic fibrosis (CF). It is speculated that they represent a marker of the chronic endobronchial infection and sustained inflammatory response in CF. Our aim was to evaluate whether azithromycin (AZM), through its antiinflammatory effect, could affect the level of BPI-ANCA in CF patients. Eighteen patients with CF aged 5.5-36.3 years (median 15.1) were enrolled in a randomised, double-blind, placebo-controlled trial of AZM (250 mg twice a week to 10 patients) or placebo (8 patients) for 12 weeks. BPI-ANCA levels were recorded pre- and post-treatment and compared to a group of 18 matched healthy controls. Chi-square analysis, Kruskal-Wallis and Mann-Whitney tests were used to compare between the groups. Pre- and post-treatment values were compared using the Wilcoxon Signed-Ranked test. BPI-ANCA was found in 12 CF patients (67%) and four (22%) healthy subjects (P<0.001). The mean BPI-ANCA level was 3.94+/-6.15 U/ml (mean+/-SD) in healthy subjects and 38.11+/-42.34 U/ml in CF patients (P=0.023). The mean BPI-ANCA level was higher in patients with Pseudomonas aeruginosa compared to those without (64+/-35 U/ml and 25+/-41 U/ml respectively, P=0.032). No change in BPI-ANCA levels occurred in the AZM-treated patients [35 (0-127) U/ml (median (range) and 30 (0-120) U/ml, respectively] or in the placebo group [10 (0-66) U/ml and 13 (0-83) U/ml, respectively]. BPI-ANCA levels are significantly higher in patients with CF compared to healthy controls. BPIANCA levels are higher among patients colonised with P. aeruginosa. Twelve weeks of AZM therapy did not lower the BPI-ANCA level in patients with CF.