Bactericidal activity of human beta-defensin 3 (hBD-3) against Streptococcus mutans and Actinobacillus actinomycetemcomitans was inhibited in a dose-dependent manner by the presence of saliva and/or serum. Increasing the concentration of hBD-3 partially overcame this inhibition. A fast bactericidal effect was observed against both bacterial strains, suggesting a potential therapeutic use for hBD-3 in the local treatment of oral infections.