The mechanisms involved in the differential regulation of airway immune responses in atopic versus non-atopic individuals are poorly understood, In this study, the association between non-specific immunity and the differential airway antigen-specific immune responses was examined in a murine model. The disparity in antigen-specific IgE and IgG2a productions between the two strains of mice was observed to be significant, C57BL/6J mice were much more efficient than BALB/cJ mice in making IgE antibody to inhaled ovalbumin (OVA) antigen, On the contrary, BALB/cJ mice did make more IgG2a antibodies than C57BL/6J mice to inhaled OVA, These findings suggest that in C57BL/6J mouse strain a predominant T(h)2 type of immune response develops in response to inhaled OVA antigen. In contrast, BALB/cJ mice mount a T(h)1 type of immune response to aerosolized OVA antigen, Furthermore, after lipopolysaccharide (LPS) stimulation, the IL-12 mRNA expression of lung-derived cells from BALB/cJ mice was higher than that from C57BL/6J cells. However, the lung-derived cells of C57BL/6J mice stimulated by LPS produced higher levels of IL-10 and prostaglandin E(2) than BALB/cJ lung-derived cells did. Therefore, our study demonstrated that the difference of lung-derived cells in their ability to produce cytokine and prostaglandin between BALB/cJ and C57BL/6J mice correlates well with the type of the airway antigen-specific immune effector functions.