We investigated the effect on specific antibody response of naive and sensitized mice orally administrated with low (0.25 mg) or high (10.0 mg) doses of Dermatophagoides pteronyssinus (Dp) extract. We also examined the effect of oral administration of Dp on the production of autoantibodies to immunoglobulin G (IgG) and immunoglobulin E (IgE). Naive and sensitized mice both showed a marked down-regulation of IgE antibody production, regardless of the dose of Dp. We also detected an inhibitory effect of the total IgE levels and the allergen-specific IgG1, IgG2a and IgG2b antibody response in sensitized mice given the low dose of Dp. In contrast, high doses of Dp stimulated IgG1 antibody production in both naive and sensitized animals. In addition, the oral tolerance induction protocol stimulated anti-F(ab′)2γ and anti-Fcγ autoantibody production. Evaluation of IgG anti-IgE autoantibodies by a direct enzyme immunoassay (EIA) revealed the presence of these autoantibodies, predominantly of the IgG1 isotype, specifically in those animals fed with the high dose. In contrast, IgG-IgE complexes, determined by EIA using immobilized anti-IgE antibodies, were detected mainly in sera of control animals. The autoantibody anti-IgE specificity was tested against IgE-TNP and IgE-DANSYL murine proteins and revealed different inhibition profiles, suggesting the action of heterogeneous subpopulations of autoantibodies. Taken together, our results show that the oral tolerance protocol with Dp was able to modulate the production of allergen-specific IgE antibodies in both naive and sensitized animals. In addition, we suggest that anti-IgE autoantibodies participate in the modulation of allergic response triggered by oral tolerance protocols.