We characterized the immune response in humans after vaccination with a Pseudomonas aeruginosa immunotype 5 O-polysaccharide (O-PS)-toxin A conjugate vaccine. The majority of volunteers responded with an immunoglobulin G (IgG) antibody response on enzyme-linked immunosorbent assay (ELISA) to both the toxin A and the lipopolysaccharide (LPS) components of the vaccine. Maximal titers to both vaccine components were seen 42 days after immunization. Antibody levels remained elevated for at least 14 months after vaccination. The anti-LPS IgG response was predominantly within the IgG1 and IgG2 subclasses, whereas the antitoxin A response was within the IgG1 subclass. There was a gradual elevation of IgG4 antitoxin antibody, with maximal levels seen at 14 months after immunization. No concomitant IgG4 antibody rise to LPS was observed. Immunization evoked a vigorous IgA1 and IgA2 antibody response to LPS, which was long-lived. Only a modest, transient IgA antitoxin A response was noted. Both antitoxin A--neutralizing and opsonic antibodies were elicited by immunization and remained elevated over the 14-month postimmunization period studied.