AbstractSpecific responses toStaphylococcus aureus (S.aureus)were assessed to prove a decrease or defect of specific protection againstS.aureusin patients with hyper‐IgE syndrome (HIES). Interleukin‐1 (IL‐1) production, interleukin‐2 (IL‐2) production and response to IL‐2 were studied in three groups (A —patients with HIES, B — control patients withS.aureusinfections, C — healthy controls). When lymphocytes or monocytes (Mo) were stimulated by lectins, there was no difference in the three groups. In the experiments concerning IL‐1 derived from Mo activated byS.aureus, the proliferation of cultured fibroblasts showed higher levels of DNA synthesis in the A or B group than in the C group. The IL‐2 derived from peripheral blood lymphocytes (PBL) activated byS.aureusshowed higher levels of activity in the B group than in the A or C group. The response to IL‐2 in the A group was decreased as compared with the C group, and a control patient aged 7 years showed the highest level of all subjects. When PBL were activated byS.aureusas a specific antigen, both IL‐2 production and response to IL‐2 showed lower levels of activity in the A group than in the B group.These results indicated that there was a defect or decrease of specific protection againstS.