Allergic disorders are mediated by T lymphocytes secreting T helper 2 (Th2) cytokines, interleukin-4 (IL-4) and interleukin-5 (IL-5), resulting in high levels of serum immunoglobulin E (IgE) and recruitment of eosinophils. One of the treatment strategies is to downregulate the Th2 component by inducing a T helper 1 (Th1) response to the relevant allergen, because Th1 and Th2 cytokines are thought to be mutually antagonistic. In this study, we examined the effects of Mycobacterium vaccae, a potent inducer of Th1 immunity, on allergic responses in a murine model. A single injection of M. vaccae into ovalbumin (OVA)-preimmunized BALB/c mice suppressed serum IgE over a wide dose range (10(7), 10(8) or 10(9) M. vaccae). Further experiments, using 10(7) M. vaccae injected twice, showed that this treatment inhibited not only serum IgE, but also the potential for ovalbumin-induced IL-5 production by spleen cells. This non-specific ability of a mycobacterium to decrease Th2 activity, even when not presented together with the allergen, is in agreement with recent epidemiological studies on the impact of bacillus Calmette-Guérin (BCG) vaccination, and of other potent Th1 stimuli, on the incidence of atopy. The suppression of serum IgE and allergen-specific IL-5 synthesis by M. vaccae suggest that this organism is likely to have clinical application in the immunotherapy of allergy.