Patients chronically colonised by P. aeruginosa develop a pronounced antibody response against P. aeruginosa that can be used to discriminate between superficial colonization and chronic infection. Anti-P. aeruginosa antibodies fail to afford protection against this pathogen; moreover high levels of antibodies are correlated with a poor prognosis. We investigated the significance of anti-P. aeruginosa antibodies (precipitins) by crossed immunoelectrophoresis (CIE) in 94 patients attending the Cystic Fibrosis Center of Florence. The highest numbers of precipitins were found in serum from patients chronically colonized in comparison to those patients who were transiently or not colonized. A negative correlation was found between the number of precipitin peaks and clinical conditions, evaluated with Schwachman score, and the number of precipitins and pulmonary functions. In summary, anti-P. aeruginosa antibodies fail to protect against P. aeruginosa bronchopulmonary infections, and are correlated to a more severe disease. Based on our experience, P. aeruginosa antibodies can be considered a reliable index of lung damage.