Whole-cell pertussis vaccines have been shown to selectively induce T helper 1 (Th1)-type responses in human and animals. In this study, we investigated whether whole-cell B. pertussis could inhibit allergic airway reactions in a murine model of asthma induced by ovalbumin (OVA). Systemic administration of whole-cell B. pertussis strongly inhibited allergic airway reactions such as eosinophil recruitment into the airway, lung inflammation, and airway hyperresponsiveness to methacholine. The inhibitory effect of whole-cell B. pertussis was mediated by chromosomal DNA and pretreatment of DNA with CpG methylase or DNase I resulted in a loss of the inhibitory effect. Treatment of animals with B. pertussis DNA significantly decreased the Th2 cytokine (interleukins IL-4 and IL-5) concentrations in the airways without increasing Th1 cytokines. These results suggest that B. pertussis DNA containing unmethylated CpG appears to be responsible for the inhibitory effect of whole cell B. pertussis on the allergic airway reactions through inhibition of the Th2 response.