The aim of this study was to investigate whether the effect of bacillus Calmette-Guérin (BCG) immunization on ovalbumin-induced allergic inflammation in a rat model depends on the genetic predisposition to react with a T helper cell (Th) 2-type cytokine response. This study was performed in an inbred Th2-predisposed "asthma prone" rat strain (brown Norway [BN]) and in an outbred nonpredisposed strain (Sprague Dawley [SD]), to differentiate between genetic and environmental factors. BCG decreased numbers of lung eosinophils and macrophages in the SD rat. This effect was not seen in the BN rat. In the BN rat, but not in the SD rat, BCG downregulated levels of total serum IgE. No significant differences were found with respect to frequencies of IFNgamma- or interleukin-4-producing cells in the lung in both rat strains. These results indicate that the degree and pathway of immunomodulatory effect of BCG in two genetically different rat strains is dependent on the genetic predisposition to develop a Th2-type response. Therefore, differences in genotype in relation to environment may result in difference in involvement of contributing pathogenic factors and thus different responsiveness to therapeutic strategies.