Two strains of interleukin-4 (IL-4) gene knockout mice were studied and compared with wild strains to determine the role of IL-4 in the immunopathogenesis of murine allergic aspergillosis. Animals immunized intraperitoneally were subsequently challenged with Aspergillus antigen intranasally. The animals were evaluated for total serum immunogolulin E (IgE) levels, Aspergillus-specific IgG antibody isotypes, peripheral blood eosinophils, cytokine and chemokine mRNA transcripts in spleen cells, and pulmonary histology. No serum IgE was detected in animals deficient in the IL-4 gene. Aspergillus-specific IgG(1) was detected in all animals, while enhanced revels of IgG(2a) were detected in IL-4 knockout animals challenged with A. fumigatus antigen. There were no differences in the peripheral blood or lung eosinophils in the two groups of mice exposed to A. fumigatus. These results indicate that lung injury in Aspergillus-antigen challenged animals may be the result of the eosinophil mediators and that IgE-mediated injury may not be significant in this model, which may be a significant variation between the model and human allergic aspergillosis.