The early stage of the colonization of Pseudomonas aeruginosa in cystic fibrosis (CF) was investigated. Most CF patients, once they have become colonized, harboured genomically related P. aeruginosa strains in their respiratory tract over long periods. Unrelated CF patients were colonized with different strains; however, within families cross-infection between CF siblings frequently took place. Adherence tests with buccal epithelial cells demonstrated that the epithelial cell layer of the oropharynx remained intact for up to 2 years after the onset of colonization with P. aeruginosa. Among the constituents of the microcolony the bronchial mucins were determined to be the major binding targets of CF isolates of P. aeruginosa. The time course of antibody formation to outer membrane antigens of P. aeruginosa in CF serum was analysed by Western immunoblots. Lipopolysaccharide and protein H induced the first systemic immune response.