Rationale Titers of cat-specific IgE ab in sensitized patients with atopic dermatitis (AD) are markedly elevated compared to sensitized subjects without AD. In addition, T cells from patients with AD show weak proliferation to IL-10- and IFN-γ-inducing chain 2 epitopes of the cat allergen, Fel d 1. The implication is that immune control mechanisms are deficient in AD patients. We examined the relationship between IgE ab to cat and the role of the anti-inflammatory cytokine, IL-10, in AD. Methods IgE ab to cat were assayed (Pharmacia CAP) in sensitized patients with and without AD. PBMC responses (day 7) to Fel d 1 and chain 2 epitopes were measured in the presence or absence of anti-IL-10 mAb in patients expressing HLA-DR alleles predicted to bind to chain 2 epitopes. Results The mean IgE ab titer to cat was increased in sensitized patients with AD (20.9IU/ml, n=9) compared to sensitized patients without AD (4.4IU/ml, n=14)(p<0.01). In contrast to sensitized patients without AD (IgE ab <17IU/ml), blocking IL-10 failed to enhance T-cell proliferation or IFN-γ responses to chain 2 epitopes in sensitized patients with AD (IgE ab >28.5IU/ml). Furthermore, allergen avoidance was associated with diminished production of IL-10 to Fel d 1 peptides (p<0.04) in conjunction with decreased IFN-γ in AD patients (IgE ab >61.7IU/ml). Conclusion High titer IgE ab to cat is associated with a diminished capacity for IL-10 to influence T cell responses to Fel d 1, supporting a role for T-cell immune dysregulation in AD.