T helper (Th) cells play major roles in orchestrating asthmatic airway inflammation, but the molecular mechanisms controlling Th-cell recruitment to the airways remain incompletely defined. Innate immunity contributes importantly to the recruitment of effector T cells into sites of inflammation. To understand better the role of innate immune signals in the development of airway inflammation, we used a murine model in which lipopolysaccharide (LPS) contaminating the antigen is thought to trigger Toll-like receptor 4 (TLR4). To investigate the importance of the TLR4-signaling pathway in induction of lung inflammation, we compared recruitment of adoptively transferred ovalbumin-specific Th1 and Th2 cells in wild-type and TLR4 mutant (TLR4m) mice after intranasal or aerosol challenge. Intranasal challenge of TLR4m mice with ovalbumin resulted in decreased recruitment of Th1 and Th2 cells compared with that of wild-type mice. The numbers of Th1 and Th2 cells recruited to the airways of TLR4m mice were less profoundly reduced after aerosol ovalbumin challenge. Comparing the effects of altering the dose of ovalbumin with that of LPS suggested that both contribute to the magnitude of the response in wild-type mice. Our findings demonstrate the importance of both antigen and endotoxin acting in a synergistic manner in the development of airway inflammation.