Pseudomonas aeruginosa infection is a leading cause of deterioration of pulmonary function in patients with cystic fibrosis (CF). The interaction of the bacterium with CF and non-CF tracheobronchial mucins was examined to understand the biochemical basis for the high susceptibility of the lungs of CF patients to infection by P.aeruginosa. The binding of radiolabelled bacteria to pure mucins in solid-phase assays was not significantly above non-specific binding to various blocking agents, such as bovine serum albumin, Tween 20, milk powder and polyvinyl pyrrolidine. Further, there was a tendency for the bacteria to be excluded from plastic wells and membranes coated with mucin. Therefore, an indirect approach involving the binding of radiolabelled P.aeruginosa to asialo GM1 ganglioside, the putative receptor for the bacteria on tracheal cells, was used to compare the interaction of CF and non-CF mucins with the bacteria. Highly purified preparations of CF mucin were consistently better inhibitors of the binding of the bacteria to asialo GM1 ganglioside than non-CF mucin preparations. In the case of the binding of a stable mucoid strain, the difference was statistically significant (P < 0.001) at all concentrations of mucin tested. For the non-mucoid strain, the difference was significant only at the higher concentrations. Of the saccharides tested similarly, sialyl lactose and the oligosaccharide portion of asialo GM1 were found to be good inhibitors. The increased binding of the bacteria to CF mucin was further confirmed by a solution binding assay in which the binding of 125I-labelled mucin to unlabelled bacteria was determined. The binding of the bacteria to labelled CF and non-CF mucin could be inhibited by an excess of unlabelled human tracheobronchial mucin, but not by unrelated mucins, hyaluronic acid, alginic acid, bovine serum albumin and tetramethyl urea. The higher binding of CF mucin, particularly to the mucoid strain of P.aeruginosa, is interesting and provides a model system to further investigate the biochemical parameters of the interaction.