The capacity of the BmE10-5 monoclonal antibody (mAb), with specificity for the Brucella spp. M epitope, to confer protection against infection with B. abortus 2308 (A-dominant strain) has been evaluated. Injected before infection, the BmE10-5 mAb diminished the bacterial counts in spleen from week 1 to week 8 postinfection and in liver from week 4 to week 7. Thus, protection mediated by the BmE10-5 mAb, as measured by a reduction in the bacterial counts in both spleen and liver, was demonstrated from week 2 to week 8 postinfection. The humoral immune response of IgG, IgM, IgG1 and IgG3 antibodies, specific against the B. abortus 2308 smooth lipopolysaccharide, was clearly suppressed in all the mice protected with the BmE10-5 mAb, thus demonstrating the importance, in protecting against infection, of the existence in serum of M-epitope-specific antibodies at the same time the infection is acquired. The development of subcellular vaccines including the Brucella M epitope could constitute an interesting alternative to attenuated living vaccines.