Substantial progress has been made in defining a number of Pseudomonas adhesins which may be involved in the pathogenesis of respiratory infection. As yet, it is unclear which of these adhesins are primarily responsible for initiating infection in CF. The findings that CF epithelial cells have increased numbers of receptors for P. aeruginosa attachment and that CF epithelia are less highly sialylated than normal epithelial cells is consistent with a role for Pseudomonas pili in the initial recognition of asialoganglioside receptors on epithelial cells. In addition, there is ample evidence supporting the presence of several classes of non-pilus adhesins. Adherence properties of P. aeruginosa clearly vary from strain to strain and it appears likely that all potential adhesions are not equally expressed. More importantly, the regulation of the expression of these adhesins is unlikely to be constitutive. Some may be expressed only when triggered by the appropriate environmental conditions as found in vivo. In reviewing the pathogenesis of Pseudomonas infection in the CF lung, several classes of receptors must be considered. Pseudomonas infection is limited to the bronchi in CF. The organisms do not invade the bronchial tissue, but remain in the airways forming a biofilm with associated microcolonies. Thus, it would seem reasonable to expect Pseudomonas receptors within respiratory mucin. However, to date, there is little confirmatory data to support the presence of specific receptors in mucin. Alternatively, it is possible that the failure of bacterial binding to mucin components may contribute to colonization as organisms which are not efficiently cleared by muco-ciliary function may persist in the airways long enough to find or expose cryptic epithelial binding sites. This hypothesis is supported by binding studies which demonstrate decreased Pseudomonas attachment to CF as compared with normal respiratory mucins. Based on the available data, there appears to be a hierarchy of adhesin expression. Multiple ligand-receptor interactions may occur in the respiratory tract and it may be difficult to analyze the effect of secondary adhesins in the presence of what appears to be the dominant ligand, i.e. pilin. Thus, the failure to find the expected sialylated receptor for Pseudomonas attachment may be due to methodologic problems such as studying strains under conditions in which pili are well expressed and affinities for asialylated receptors predominate. This may not be the situation in vivo after the initial contact of the infecting organisms with the epithelial surface. Not only must the organism attach initially, but it must then be able to persist within the lung. Further studies, based on genetically defined mutants should help define which P. aeruginosa gene products and which components of the CF but not the normal epithelium are responsible for this unique but ultimately fatal host/bacterium interaction.