Cell-surface polysaccharide antigens of Pseudomonas aeruginosa are important determinants of pathogenicity and represent target antigens for the development of vaccines. Two major and distinct cell-surface polysaccharides are expressed by different strains of P. aeruginosa: the serotype determinant located on the O polysaccharide side chain of the lipopolysaccharide and mucoid exopolysaccharide (MEP), an antigen usually made by isolates of P. aeruginosa from patients with cystic fibrosis. The serotype determinant has been isolated in a high-molecular-weight, non-toxic, immunogenic form known as high-molecular-weight polysaccharide. High-molecular-weight polysaccharide is safe and immunogenic in humans and elicits T cell immunity to P. aeruginosa infection in animals. Purified MEP antigen has been shown to be immunogenic in animals, and patients with cystic fibrosis colonized with mucoid P. aeruginosa respond to MEP with the production of high-titered serum antibody. In spite of brisk immune responses of patients with cystic fibrosis to MEP, they are unable to deal with the chronic respiratory colonization by mucoid P. aeruginosa. An association has been established between the presence of opsonic-killing antibody to MEP and the lack of colonization of older patients with cystic fibrosis with P. aeruginosa.