The interaction between chronic infection and chronic asthma is receiving increased investigation as a factor in the pathophysiology of asthma. To further understand this interaction, we used an animal model (BALB/c mice) with a Mycoplasma pneumoniae respiratory infection. Mice were studied 3, 7, 14, and 21 d after infection. Bronchial hyperresponsiveness (BHR) was assessed by methacholine challenge and was significantly heightened in the infected mice compared with saline controls at Days 3, 7, and 14. The associated inflammatory response was mainly neutrophils. The tissue inflammatory score significantly correlated to BHR (r = 0.78, P < 0.0001). Additionally, tissue interferon (IFN)-gamma was significantly suppressed at Days 3 and 7 in the infected group compared with controls; and at Days 3, 7, and 14 compared with Day 21 in the infected group. There was a significant negative correlation between lung tissue messenger RNA levels of IFN-gamma corrected for beta-actin and BHR (r = -0.50, P = 0.022). Thus, M. pneumoniae respiratory infection is associated with BHR in this murine model. It appears that acute mycoplasma infection suppresses IFN-gamma, which may be a pivotal factor in the control of BHR.