Listeria monocytogenes colonized the gastrointestinal tract of adult germfree rats (10(10) to 10(11)/g, dry weight) within 24 h after oral exposure. Between 3 and 14 days after monoassociation, L. monocytogenes caused a self-limiting pseudomembranous colitis, bacteremia, and infection of the spleen and liver. Monoassociation of rats with Listeria for 8 weeks stimulated 32- and 4-fold increases in serum immunoglobulin A (IgA) and IgG, respectively, whereas serum IgM decreased 2-fold. The normal microbial flora was inhibitory to Listeria colonization, since L. monocytogenes was cleared from the gastrointestinal tract of formerly monoassociated rats within 20 days after conventionalization and did not colonize the gastrointestinal tract of conventional rats after intragastric instillation of 10(8) viable L. monocytogenes. Listeria-monoassociated rats delivered large litters of healthy pups whose gastrointestinal tracts were slowly colonized with L. monocytogenes. between 3 and 60 days of age, Listeria-monoassociated rat pups exhibited eight- and fourfold increases in serum IgG and IgM, respectively; however, serum IgA was elevated (16-fold) only at 9 to 15 days of age. Adult Listeria-monoassociated rats had acquired cellular resistance to intravenous challenge with L. monocytogenes. Prolonged monoassociation of L. monocytogenes in rats attenuated its virulence for conventional rats.