Lactic acid bacteria are increasingly used to restore the ecological equilibrium of different mucosal areas in humans and/or animals. Likewise, they can be used to potentially protect against pathogenic microorganisms. In the present paper, the preventive effect of intranasally inoculated Lactobacillus fermentum against challenge with Streptococcus pneumoniae was studied, using a mouse experimental model. L. fermentum inoculated four times at a dose of 10(7) colony forming units per mouse was able to decrease the number of S. pneumoniae throughout the respiratory tract. The L. fermentum treatment increased the number of activated macrophages in lung slices, and a higher lymphocyte population in the tracheal lamina propria. S. pneumoniae challenge showed a typical response against pathogen with a higher non-specific immune response. Preventive treatment, i.e. L. fermentum administration prior to S. pneumoniae challenge, showed a response close to that of L. fermentum. Anti-S. pneumoniae antibodies increased in lactobacilli-treated animals compared to the non-treated lactobacilli mice. The increase in the antibody levels suggests that the mucosal immune system could be involved in the protective effect, accomplished with competitive exclusion, nutrient competition and production of inhibitory substances. This paper will be the basis for further studies of the protective effect of lactobacilli against S. pneumoniae in the respiratory tract.