Tularemia is caused by the facultative intracellular bacterium Francisella tularensis. Attenuated live vaccines, such as F. tularensis LVS (live vaccine strain), afford good--although not complete--protection; how to judge the degree of this protection has long been a problem. Both natural infection and vaccination result in immunospecific and long-lasting humoral and cell-mediated immunity. The latter is the crucial protective mechanism, whereas the humoral response protects only against strains of reduced virulence, such as those used in the vaccines. Immune serum has been used to screen for structures of F. tularensis with the ability to induce a protective immune response. This immune serum is, however, primarily directed toward antigens different from those involved in cell-mediated immunity. Serum antibodies from primed individuals recognize carbohydrate capsule antigens of F. tularensis, whereas T lymphocytes recognize membrane polypeptides of the organism. The preparation of membrane polypeptides from F. tularensis is now facilitated by the availability of a capsule-deficient mutant of F. tularensis LVS. In vitro, several membrane polypeptides of the mutant stimulate T lymphocytes from vaccinees and from naturally infected individuals. Further studies of the mechanisms of induction of protective immunity should focus on these membrane polypeptides.