P6, a 16,600-dalton outer-membrane protein of Haemophilus influenzae, possesses many characteristics desired of a vaccine candidate. The protein is present in all strains of H. influenzae tested by analyses of outer-membrane protein profiles and with a monoclonal antibody. P6 is surface-exposed, as demonstrated by immunostaining techniques. Studies using monoclonal and polyclonal antisera indicate that P6 is a highly conserved antigen on the outer membrane of H. influenzae. Finally, experiments using affinity chromatography and normal human serum establish that P6 is a target of human bactericidal antibodies. The gene encoding P6 has been isolated and cloned into Escherichia coli, an accomplishment that will facilitate molecular analysis of the role of P6 in human immunity to H. influenzae.