We have characterized the cell‐mediated and humoral immune response of patients with atopic dermatitis (AD) and healthy controls in response to two novel staphylococcal antigens (NP‐tase, p70) and the superantigen staphylococcal enterotoxin B (SEB). The parameters studied were IgE, interleukin (IL)‐4 and interferon (IFN)‐γ synthesis by peripheral blood mononuclear cells (PBMC) after stimulation with NP‐tase, p70 and SEB in vitro. Both antigens, as well as SEB, induced IL‐4 and IFN‐γ secretion in patients and controls. However, patients with AD showed a significantly diminished IFN‐γ production in response to NP‐tase or SEB. Furthermore, we demonstrated a good correlation between antigen‐stimulated IgE production and the IL‐4/IFN‐γ ratio in vitro. A distinct subgroup of PBMC showed impaired IFN‐γ synthesis and enhanced IL‐4 secretion after incubation with p70 or NP‐tase. These data support evidence that a subgroup of patients with AD, synthesizing low levels of IFN‐γ after stimulation with staphylococcal antigens, may have impaired abilities to clear Staphylococcus aureus colonization. Persistent staphylococcal antigens could then be responsible for inflammatory and allergic skin reactions in patients with AD. We therefore conclude that, besides superantigens, staphylococcal antigens may also play a part in the pathogenesis of AD.