The results of the work done from the beginning of the century up to the present were reviewed, leading to the conclusion that the large amount of available knowledge on the chemistry, immunological, antigenic, and biological aspects of the antigens of Salmonella, was not sufficient to determine which antigen(s) accounted for immune protection on systemic salmonellosis. Data accumulated on numerous and diversified preparations being used as immunogens, as well as on several experimental models and different methods of studying the immune response. In relation to Salmonella typhi, given that this microorganism is an exclusive natural pathogen only for man, the results of protection obtained with laboratory animal experiments, often, did not show any correlation with observed facts in the human being. It should be mentioned, however, that the search for an immune response has been restricted, in most instances to the 0,H and Vi antibodies, and to active or passive protective tests with mice. Cell mediated immunity has been evaluated mainly by using skin tests with chemically ill defined and variable protein preparations. No definitive hypothesis is available, at present, related to the mechanism(s) of immune protection operating on systemic salmonellosis.