Specific pathogen-free C57B1 mice are 100 to 1,000 times as sensitive as CD-1 mice to intravenous or oral challenge by Salmonella enteritidis or S. gallinarum. Resistance to infection by S. pullorum was unaffected. Growth of Listeria monocytogenes and Mycobacterium bovis (BCG) in intravenously infected C57B1 mice was similar to that seen in CD-1 mice. Quantitative counts of viable S. enteritidis in the walls of the stomach, small intestine, cecum, and large intestine and in the corresponding intestinal contents showed that most of the oral challenge inoculum was rapidly inactivated so that, by 24 hr, less than 1% was still viable. Overnight starvation and pretreatment with bicarbonate solution increased the relative survival of the challenge approximately 10-fold. Despite the rapid and extensive inactivation of the oral inoculum within the normal intestine, significant numbers of salmonellae reached the liver and spleen by 48 hr, and this systemic infection was subsequently responsible for the death of a high proportion of the challenged animals.