OBJECTIVE To study the effects of Mycobacterium vaccae (M. vaccae) on the lung function, airway hyperresponsiveness and airway inflammation in a guinea pig model of asthma. METHODS Asthma was induced with ovalbumin (OVA) in 71 guinea pigs. The changes of lung resistance (R(L)) and dynamic lung compliance (C(dyn)), the accumulation of inflammatory cells in bronchoalveolar lavage fluids (BALF), and the contraction reaction curve of tracheal smooth muscles to carbachol in vitro were determined. RESULTS Pretreatment with M. vaccae as a single dosage by intramuscular injection (i.m) inhibited the early phase of asthma in the sensitized guinea pigs in a dose-dependent manner. R(L) (1 min to 15 min) increased 46.4% in the 2.5 micro g group, 29.6% in the 7.5 micro g group, and 20.8% in the 22.5 micro g group, which were significantly lower than that in the model control group (95.3%) (P < 0.05 approximately 0.01), respectively. The mean decrease of C(dyn) was 26.8% in the 2.5 micro g group, 23.5% in the 7.5 micro g group, and 21.5% in the 22.5 micro g group, which were significantly lower than that in the model control group (38.7%) (P < 0.05), respectively. Pretreatment with M. vaccae in a dosage of 2.5 micro g, 7.5 micro g and 22.5 micro g (per guinea pig) i.m also inhibited the late phase of asthma. The total white blood cells in BALF was (16.2 +/- 3.2) x 10(8)/L in the 2.5 micro g group, (14.6 +/- 3.4) x 10(8)/L in the 7.5 micro g group, and (15.4 +/- 2.5) x 10(8)/L in the 22.5 micro g group, which were significantly lower than that in the model control group (22.3 +/- 2.2) x 10(8)/L (P < 0.01 approximately 0.001), respectively. BAL eosinophil count was (11.6 +/- 3.0) x 10(8)/L in the 2.5 micro g group, (6.0 +/- 1.5) x 10(8)/L in the 7.5 micro g group, and (2.2 +/- 1.7) x 10(8)/L in the 22.5 micro g group, which were significantly lower than that in the model control group (15.9 +/- 5.2) x 10(8)/L (P < 0.01 approximately 0.001), respectively. M. vaccae significantly inhibited carbachol-induced airway hyperresponsiveness in the tracheal smooth muscle (TSM) from the sensitized guinea pigs. EC(50) (the concentration of carbachol required to increase TSM contraction value by 50% from the baseline) was 0.140 micro mol/L in the 2.5 micro g group, 0.179 micro mol/L in the 7.5 micro g group and 0.236 micro mol/L in the 22.5 micro g group, which were higher than that in the model control group (0.038 micro mol/L). CONCLUSIONS M. vaccae was found to improve lung function, inhibit airway inflammation and airway hyperresponsiveness in this animal model, which supports its application in the treatment of asthma.