Suckling and adult mice were infected intragastrically with different doses of viable Listeria monocytogenes. The 50% lethal dose for the intragastric infection was 10(3.7) CFU for suckling mice, while adult mice were highly resistant and the 50% lethal dose was more than 10(9.3) CFU. When adult mice were infected intragastrically with 5 x 10(8) CFU of L. monocytogenes, no mice died. However, 35% of adult mice died when they were treated with cyclosporin A 1 day before infection. Although mice did not die when treated with an L. monocytogenes-resistant broad-spectrum cephalosporin, sodium cefbuperazone, before and during infection, the number of L. monocytogenes bacteria increased in the feces. The sodium cefbuperazone treatment of mice resulted in superinfection, i.e., a marked decrease of Escherichia coli and an increase of Enterococcus spp. in the intestines. Furthermore, host resistance against the intragastric infection markedly decreased when the mice were treated with both drugs. The growth of L. monocytogenes was augmented in the spleens, mesenteric lymph nodes, Peyer's patches, and feces, and the mortality of the mice was 65%. These results suggest that both cellular immunity and the intestinal bacterial flora are required for host resistance against oral L. monocytogenes infection.