The hypothesis that a lack of early childhood bacterial infections would favor the development of allergic disease suggests that bacteria can be used as a potential treatment for allergic asthma. Therefore, in this study, we investigated the therapeutic potential of heat-killed Mycobacterium vaccae in two mouse models of allergic asthma. For this purpose, mice were sensitized i.p. with ovalbumin/alum (severe model) or ovalbumin alone (mild model) and challenged on days 77, 80 and 83 by inhalation of either ovalbumin or saline aerosols. Treatment of mice with M. vaccae (s.c. 10(7) or 10(8) colony-forming units) on days 56 and 63, however, did not reduce airway hyperresponsiveness and eosinophilia, IgE and interleukin-5 production 24 h after ovalbumin challenge in either mouse model. We therefore conclude that treatment of sensitized mice with M. vaccae before allergen exposure is not able to reduce the allergic and asthma-like response in a mild and a severe model of allergic asthma.