BACKGROUND: Both Bacille Calmette-Guerin (BCG) vaccine and dehydroepiandrosterone (DHEA) have a suppressive effect on asthma. OBJECTIVE: To evaluate the effect of BCG and DHEA combination against the development of asthma. METHOD: Female BALB/c mice were sensitized and provoked with ovalbumin (OVA). One week before sensitization, BCG(1*10(5) CFUs) was administered intraperitoneally and the animals were fed with a diet incorporated with 0.01% (w/w) of DHEA for 4 weeks. Methacholine brochoprovocation tests and bronchoalveolar lavages (BAL) were carried out. RESULT: As compared with control, the combined BCG and DHEA treatment significantly suppressed both maximal airway resistance expressed as enhanced pause (P<0.01) and airway hypersensitivity (35.0 vs. 10.2 mg/mL, P<0.05) to methacholine, and BAL fluid eosinophilia (1.4+/-0.3 vs. 10.7+/-1.4%, P<0.001); however, the combination was not superior to each treatment. The level of IFN-gamma in splenocyte supernatant was significantly higher in the combined group than that in control group (295.1 vs. 218.8 pg/mL, P<0.05). CONCLUSION: A combined BCG and DHEA treatment suppresses the development of airway hyperresponsiveness and eosinophilic inflammation along with increased Th1 response in OVA-induced asthma mice. However, there is no beneficial effect of the combination above each.