Although capsular polysaccharide-based vaccines are effective at reducing the incidence of meningococcal disease caused by serogroups A, C, Y, and W135 (1 –3 ), immunization against serogroup B disease using similar strategies has proven unsuccessful (4 ,5 ). The primary reason for this is that the α2,8-linked N -acetylneuraminic acid homopolymer expressed by serogroup B strains is poorly immunogenic in humans (6 ). Consequently, considerable effort has been devoted towards the development of alternative strategies for vaccination against serogroup B disease. Many of these newer strategies include the use of lipooligosaccharide (LOS) as a protective antigen (7 ). One of the approaches that we are currently pursuing involves the use of synthetic oligopeptides to stimulate antibody responses that are cross-reactive with LOS antigens expressed by serogroup B Neisseria meningitidis strains. An integral part of these studies has been the application of combinatorial phage-display technology. Described here is an overview of the methods that we have utilized to identify peptide mimics of LOS epitopes.