BACKGROUND: We developed a Pseudomonas aeruginosa outer membrane protein(OMP) vaccine, CFC-101, and the prophylactic efficacy of which has been demonstrated in animal models. In order to evaluate the safety and immunogenicity of the P. aeruginosa vaccine, we carried out a phase I/IIa clinical trial in healthy male volunteers. METHODS: Groups of eight volunteers, including two placebo subjects, were vaccinated intramuscularly with three doses of 0.25, 0.5 or 1.0 mg of the vaccine at one week intervals. Signs of systemic and local reactions observed after vaccination were recorded for each vaccinee for 5 days. Physical examinations were performed on days 0, 1, 7, 8, 14, 15, 21, and 42, and clinical laboratory tests were done on days 0, 3, and 21. Blood samples for assay of serum antibody levels were obtained up to 42 days after the first vaccination. RESULTS: The vaccine was generally well tolerated by all vaccinees, showing no significant side effects. In the three dosage groups, all vaccinees, except one receiving the 0.25 mg dose, showed significant elevation in serum IgG antibody titers against the vaccine proteins, indicating 100% seroconversion in 0.5 and 1.0 mg groups. The human antibodies induced by the vaccine were specific for P. aeruginosa OMPs, as confirmed by western blot analysis and immunoprecipitation assays. The capacity of the human antisera to enhance opsonophagocytic killing activity by polymorphonuclear leukocytes and to confer protection against P. aeruginosa infections indicates that the antibodies elicited by the vaccine have protective efficacy. CONCLUSION: We conclude that the P. aeruginosa OMP vaccine is safe and effective for human use and its optimal dose to be 0.5 or 1.0 mg.