The recombinant soluble form of the human high-affinity receptor for IgE alpha subunit (sFc epsilon RI alpha) is able to block the binding of IgE to the cell surface Fc epsilon RI and prevent the activation of mast cells and basophils. To evaluate its anti-allergic effects in vivo, we established a novel model for type I allergy by transplanting antigen-specific IgE-secreting hybridomas into syngeneic mice. The hybridomas continuously produced anti-2,4,6-trinitrophenyl IgE in vivo, and ear swelling responses could be elicited upon applying picryl chloride to the ears of these mice, which reached their maximum 1-2 h after the antigen challenge. The second swelling response, in extent comparable to the first response, was induced by the second antigen challenge several days later. When the sFC epsilon RI alpha was intravenously administered before the first challenge and periodically between the first and the second challenges, the ear swelling response to the second challenge, but not to the first challenge, was suppressed almost completely. Immunohistochemical examination revealed that treatment with the sFc epsilon RI alpha blocked the binding of IgE to the cell surface IgE receptors after the first challenge. Thus, our results indicate that the sFc epsilon RI alpha suppresses recurrent allergic reactions by preventing IgE binding to the cell surface Fc epsilon RI.