The majority of asthma exacerbations are caused by respiratory infections, with rhinovirus (RV) being the most common virus. Recent evidence has suggested that decreased generation of IFN-gamma is associated with more severe colds and delayed elimination of virus. Whether the generation of IFN-gamma also has any relationship to general features of asthma severity has yet to be determined. To evaluate this hypothesis, peripheral blood mononuclear cells from 19 subjects with atopy and asthma were incubated with RV16 for 6 days to determine IFN-gamma and interleukin (IL)-5 production; these responses were then compared with measurements of airflow obstruction and airway responsiveness. RV16-induced IFN-gamma production correlated significantly with the methacholine PD (r = 0.50, p = 0.03), and the ratio of RV16-induced IFN-gamma:IL-5 correlated with % predicted FEV1 (r = 0.53, p = 0.02). In contrast, there were no significant associations between measures of asthma severity and RV-induced IL-5. These findings suggest that a cytokine imbalance with a deficient Th1 response to RV, but not a Th2 response, is associated with measures of asthma severity and support the concept that impaired antiviral responses may be associated with asthma severity.