Immunization with avirulent Salmonella typhimurium strain SL3235, a smooth, aroA derivative, was shown to induce high levels of resistance to challenge with virulent S. typhimurium in innately hypersusceptible C3H/HeJ mice and inherently resistant C3H/HeNCrlBR mice. Strain SL3235 is one of a class of avirulent aroA-derivatives made from various strains and species of SalmoneUla that are being considered as vaccine candidates for cattle and humans. This paper supports their efficacy and potential utility in this regard. In C3H/HeJ mice, immunity against over 1,000 50% lethal doses of virulent S. typhimurium was evident as early as 3 days after immunization and persisted for at least 7 months. Further, the vaccine was effective over a broad * Corresponding author. immunity against challenge with virulent S. typhimurium strains in both mouse strains. In addition, short-term crossprotection against Listeria monocytogenes is evident. The period of nonspecific resistance is accompanied by marked splenomegaly. Immune macrophage-rich fractions, but not immune T cells, were able to transfer protection into naive C3H/HeJ recipients. MATERIALS AND METHODS Mice. Female C3H/HeJ and C3H/HeNCrlBR mice, 8 weeks old, were purchased from Jackson Laboratories, Bar Harbor, Maine, and Charles River Laboratories, Wilmington, Mass., respectively. They were housed in plastic cages with Absorb-Dri for bedding. Purina Mouse Chow and fresh water were available ad libitum. Bacterial strains. S. typhimurium strain SL3235, aroA-(nonreverting), was obtained from Bruce Stocker, Depart