Seven Lactobacillus strains belonging to four species were evaluated for pathogenicity as well as for in vitro sensitivity to the bactericidal mechanisms of macrophages in a rabbit infective endocarditis (IE) model. Two bacteremia-associated strains, L. rhamnosus PHLS A103/70 and L. casei PHLS A357/84, as well as the L. rhamnosus type strain and the probiotic L. rhamnosus strain ATCC 53103, showed moderate infectivity, and the virulence of the probiotic L. casei strain Shirota and type strains such as L. acidophilus ATCC 4356(T) and L. gasseri DSM 20243(T) in the model was negligible. The strains that showed pathogenic potential in the rabbit IE model (PHLS A357/84, PHLS A103/70, and ATCC 53103) were more resistant than strain Shirota to intracellular killing activity by mouse macrophages in vitro and also to bactericidal nitrogen intermediates, such as nitric oxide and NO(2)(-) ions. These results suggest that resistance to host innate defense systems, which would function at inflammatory lesions, should be considered in the safety assessment of Lactobacillus strains.