Salmonella enteritidis is highly virulent for the mouse causing an infection resembling mouse typhoid. Survivors of the infection are completely resistant to reinfection and eliminate a large challenge dose of virulent organisms within 72 hr. The antigenically related Salmonella gallinarum was almost avirulent for the mouse but animals vaccinated with this organism were equally capable of eliminating a lethal dose of virulent S. enteritidis. Living Salmonella pullorum, on the other hand, was quickly eliminated from the tissues of normal mice. Vaccination with this organism failed to evoke an effective bactericidal mechanism. Alcohol-killed vaccines of these three Salmonellae all produced an increase in blood clearance rate, but gave only marginal protection against S. enteritidis. Liver and spleen counts on these mice revealed a 1 to 2 day delay before any net increase in the total bacterial population could be observed. Immunization of mice with increasing doses of living Salmonella montevideo resulted in progressively greater killing of a challenge dose of S. enteritidis despite the absence of common somatic antigens between the two strains. The degree of protection varied with the size of the residual population of S. montevideo in the vaccinated mice. The significance of these findings in assessing the importance of various factors involved in the development of acquired resistance to Salmonella infections is discussed.