Background: Immunotherapeutic approaches to allergy consist of reliably changing allergen-specific T_H2 immunity associated with secretion of IL-4, IL-5, and IL-13, along with IgE antibodies in atopic individuals to T_H1 immunity. Our earlier data show that targeting of protein antigens to antigen-presenting cells (APCs), such as macrophages, by means of scavenger receptors (SRs) results in a pronounced T_H1 immunity. Here we demonstrate a novel experimental approach for the conversion of T_H2 immunity to T_H1 immunity by using SR delivery of allergens. Objectives: We sought to show that targeting of allergens by means of SRs to APCs triggers T_H1 immunity and that an established T_H2 immunity to the Der p 1-immunodominant peptide 111-139 (p1, 111-139) can be modulated to a nonallergic T_H1 phenotype. Methods: Analysis of the T cell-derived cytokines IL-4, IL-5, IL-13, and IFN-γ in response to p1, 111-139 in C57BL/6 mice 7 to 42 days after immunization, measurement of specific antibody responses, eosinophilic infiltrate, and skin hypersensitivity in response to allergen challenge constitute the parameters of in vivo immunity. Results: We show that p1, 111-139, when delivered to APCs by means of SR, elicits a T_H1-dominant immunity. If it is delivered to APCs either after chemical coupling to SR ligands or by means of mere coadsorption on alum in the presence of an SR ligand, the established T_H2 immunity can be modified to T_H1 immunity. Conclusions: SR-mediated delivery of allergens has immunotherapeutic potential that may be usable in atopic individuals. (J Allergy Clin Immunol 2002;109:321-8.)