The vaccine potential of the Neisseria meningitidis lactoferrin-binding proteins LbpA and LbpB was evaluated. Sequencing and sequence alignments suggested that LbpA is relatively well conserved with variability largely restricted to two surface-exposed loops in a proposed topology model. Consistently, antisera raised against synthetic peptides corresponding to exposed loops generally recognized the LbpA proteins of many different strains. Hence, LbpA was considered an attractive vaccine candidate. LbpB shows a higher degree of sequence variability. For immunisation studies, LbpA was overproduced in N. meningitidis and a histidine-tagged LbpB protein was produced in Escherichia coli. Outer membrane vesicles carrying overproduced LbpA and purified LbpB were used to immunise laboratory animals. The bactericidal activity and cross-reactivity of the antibodies was evaluated using meningococcal strains of various clonal lineages. In addition, LbpB-specific monoclonal antibodies were analysed by Western blots and whole-cell enzyme-linked immunosorbent assays. Our results show that both proteins are immunogenic and able to induce bactericidal antibodies, but that the cross-reactivity of these antibodies is limited.