Background: The maternal immunologic experience associated with early life exposure to allergens might contribute to the development of allergy during infancy. Objectives: We sought to analyze the effect of the mother's immunization before conception with the dust mite Dermatophagoides pteronyssinus on the allergen priming and hypersensitivity response in early immunized offspring. The kinetics of D pteronyssinus immunization were observed from newborn to adult age, and the secondary response to D pteronyssinus was followed in offspring immunized in early life. Methods: Female A/Sn mice were immunized or not with D pteronyssinus and mated with male C57BL/6 mice. The hybrid offspring were immunized to investigate allotypes and subclasses of anti-D pteronyssinus antibody, as well as total IgE levels, by using ELISA and anti-D pteronyssinus IgE antibody by using the passive cutaneous anaphylaxis reaction. Ovalbumin was used for heterologous immunization. Cytokines were measured in the cell-culture supernatant by means of ELISA, and CD4⁺CD25⁺ cells were analyzed by means of flow cytometry. Results: Offspring from immune mothers have not shown evidence of prenatal or postnatal allergen priming with respect to humoral level. Immunization with D pteronyssinus of offspring at very early life and in the postweaning period inhibited anti-D pteronyssinus IgE and IgG1 antibody production, along with the expected presence of maternal antibody. Furthermore, offspring antibody responsiveness from immune mothers has remained quiescent on secondary allergenic challenge. This maternal influence on the offspring antibody response was specific to D pteronyssinus because the immunization with a heterologous antigen did not alter IgE response. Maternal D pteronyssinus immunization induced a significant decrease of the IFN-γ level in the offspring, avoided an exacerbation of T_H2 cytokine secretion, and, concomitantly, upregulated the number of CD4⁺CD25⁺ T cells. Conclusion: Maternal immunization to D pteronyssinus seems to protect offspring from the development of allergy. (J Allergy Clin Immunol 2003;111:269-77.)