Children with milk allergy who tolerate heat-denatured milk (HM) have less severe reactions and outgrow the condition earlier than those who react to HM, which might be related to differences in IgE-dependent effector cell function.We sought to apply a novel assay to test the hypothesis that HM-tolerant children have suppressed IgE-mediated basophil responses.Allergic, HM-tolerant, outgrown, or control subjects were defined based on oral food challenges. Whole blood cells were stimulated in vitro with a range of milk allergen doses in the presence or absence of autologous serum or with dilutions of autologous serum. Activated basophils were identified by means of flow cytometry as CD63 bright CD123 + CD203c + HLA-DR − CD41a − .HM-tolerant subjects' basophils were significantly less responsive to milk allergen stimulation at all doses than were basophils from HM-reactive (allergic) individuals. In the absence of autologous serum, HM-tolerant subjects' basophils were significantly more reactive at low allergen concentrations. To a lesser extent, autologous serum also inhibited IL-3– and anti-IgE–induced, but not N-formyl-methionyl-leucyl-phenylalanine–induced, responses. The allergen-specific responsiveness of HM-tolerant subjects' basophils increased with dilution of autologous serum with normal pooled serum.Children with milk allergy with a favorable prognosis have evidence of extrinsically suppressed allergen-specific effector cell reactivity.