The role of the immune system in the homeostasis of indigenous oral bacterial populations is poorly understood. In this study, we compared the evolution of the indigenous oral microbiota of specific pathogen-free athymic nude (nu/nu) BALB/c mice with that of their corresponding phenotypically normal (nu/-) littermates. We also evaluated corresponding salivary and serum antibody activities (IgA and IgG) against the predominant indigenous oral bacteria. The bacterial species recovered from the two mouse strains were Lactobacillus murinus, Enterococcus faecalis, Streptococcus oralis and Staphylococcus epidermidis. From 27 days of age, nu/+ and nu/nu mice had significantly different proportions of oral bacterial populations. When the microbiota stabilized (at 40 days of age), the total cultivable microbiota of nu/+ mice was dominated by L. murinus (65-85%), while that of nu/nu mice was dominated by E. faecalis (40-60%). The precise factors that alter the oral resident microbiota in nu/nu mice are unknown. We found that total salivary IgA levels were significantly lower in nu/nu mice, but no association were observed between the level of salivary IgA antibody against indigenous bacteria and the proportion of these indigenous bacteria in the oral microbiota. The change in the microbiota of nude mice may have been caused by other factors such as defects in other immune functions or cold stress.