Cystic fibrosis (CF) is the most frequent life threatening autosomal recessive disease in white subjects. The primary cause of morbidity and mortality in children with CF is chronic pulmonary infection, mainly caused by Pseudomonas aeruginosa. The purpose of this studywas toassess the value of the measurement of antibodies to P. aeruginosa in diagnosing lung infection by the bacteria in CF patients.We assessed P. aeruginosa antibody titers in CF patients from Rio de Janeiro, Brazil, using cell lysate antigens aswell as recombinant PcrV, a Type III Secretion System protein. Sputum (more than 70 percent of the specimens) or oropharyngeal swabs were obtained whenever patients were regularly followed for their pulmonary disease. Blood samples were obtained with an average interval of 6 months for a period of 2 years. The ELISA cut-offs wereassigned as the positive 95 percent confidence interval of the mean antibody levels from non-fibrocysticcontrols. Our data showed that most CFpatients (81 percent) of whomwere not chronically infected by P.aeruginosa (Groups I and II), had their first serology positive for rPcrV. Cell-lysate ELISA was ableto detect P. aeruginosa antibodies before positive culture in the first serum sample of 44 percent of thepatients from Groups I and II. When serum reactivity to rPcrV and cell lysate were combined, 94 percent of CF patients from Groups I and II (n¼16) had the first serology positive for P. aeruginosa over amean time of 20 months before the first isolation of P. aeruginosa. In conclusion, longitudinal P.aeruginosa serology should become part of respiratory care follow-up, in conjunction with other lung parameter functions.