An estimated 2,500 cases of listeriosis occur annually in the United States. Listeriosis is particularly severe among pregnant women and immunocompromised individuals. Little is known regarding the effect of the food matrix on the ability of L. monocytogenes to survive in the gastrointestinal tract and cause systemic infection. Mice were inoculated with various doses of L. monocytogenes in skim milk, Half & Half, or whipping cream to determine whether differences in milk fat content influence the ability of L. monocytogenes to survive passage through the gut and infect the liver or spleen. The number of fecal samples positive for L. monocytogenes increased with increasing doses of L. monocytogenes for all three vehicles. The number of L. monocytogenes cells isolated from liver or spleen of mice dosed with L. monocytogenes was not significantly different among treatment vehicles. Dose-response models revealed that as the dosage of L. monocytogenes was increased in different milk vehicles, the number of L. monocytogenes cells in liver or spleen also increased. Although fat content of food had no dose-dependent effect on L. monocytogenes infection in the murine gastrointestinal tract, we cannot discount the possibility that it may be a factor in L. monocytogenes infections of humans because of differences in the physiology of gastrointestinal tracts of mice and humans.