SCID mice were reconstituted with purified peripheral blood mononuclear cells from patients sensitive to Dermatophagoides pteronyssinus (Dpt). After immunization with a low dose of the related allergen, these human (Hu)-SCID mice may develop a specific IgE response. By using an IgE-dependent platelet assay and the related allergen Dpt, the human IgE was demonstrated to be functional. Indeed a high correlation was obtained between both parameters. No rise in human IgE level was detected within 3 wk after the immunization with an unrelated Ag. When mice were reconstituted with peripheral blood cells from nonallergic donors and immunized with the Dpt allergen, no human IgE production was evidenced in the serum of SCID mice. However, in both allergic Hu-SCID mice (reconstituted with cells from allergic patients) or in nonallergic Hu-SCID mice (reconstituted with cells from healthy donors), an IgG response was detectable. Finally by radioallergosorbent test, a specific IgE Ab response was detected after the first allergen challenge only in allergic Hu-SCID mice. Thus, without ethical constraints, SCID mice represent a useful model for analyzing the IgE response occurring in allergic patients.