We assessed the capacity of four probiotic bacteria (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei GG, and Bifidobacterium animalis) to colonize, infect, stimulate immune responses in, and affect the growth and survival of congenitally immunodeficient gnotobiotic beige-athymic (bg/bg-nu/nu) and beige-euthymic (bg/bg-nu/+) mice. The bacteria colonized and persisted, in pure culture, in the alimentary tracts of both mouse strains for the entire study period (12 weeks). Although all adult and neonatal beige-euthymic mice survived probiotic colonization, some infant mortality occurred in beige-athymic pups born to mothers colonized with pure cultures of L. reuteri or L. casei GG. The probiotic bacteria manifested different capacities to adhere to epithelial surfaces, disseminate to internal organs, affect the body weight of adult mice and the growth of neonatal mice, and stimulate immune responses. Although the probiotic species were innocuous for adults, these results suggest that caution and further studies to assess the safety of probiotic bacteria for immunodeficient hosts, especially neonates, are required.