In order to evaluate in humans the safety and immunogenicity of a Pseudomonas aeruginosa vaccine composed of outer membrane proteins (OMPs), CFC-101, we carried out a phase I/IIa clinical trial in healthy male volunteers. Groups of six volunteers were immunized either subcutaneously (s.c.) or intramuscularly (i.m.) with three dosages of the vaccine three times at 7-day intervals. The vaccine was well tolerated by volunteers. Local reactions in the injection sites were generally mild and transient. Significant increases in OMP-specific antibody were observed in both route groups after vaccinations but was higher in the i.m.-immunized group, where vaccination with 0.5 or 1.0 mg doses yielded 100% seroconversion. The specificity of the induced antibodies to P. aeruginosa OMP was demonstrated by western blot analysis and immunoprecipitation assay. An increase in Clq-binding capacity and ability to confer mice protection from lethal challenges with P. aeruginosa indicated the protective efficacy of the elicited antibodies. Based on these data, we concluded that the P. aeruginosa OMP vaccine is safe and effective in humans with an optimal dose of 0.5 and 1.0 mg and that i.m. is the better route than s.c. for this vaccine.