Background: Recently, it has been established that CD4⁺CD25⁺ T cells with regulatory capacity are present in human peripheral blood, inhibiting allogeneic proliferation and cytokine production of preactivated CD4⁺CD25⁻ respond-er T cells. Objective: The aim of this study was to analyze in an allergen-specific setting whether such regulatory CD4⁺CD25⁺ T cells also exist and function normally in atopic individuals, especially concerning the inhibition of T_H2 cytokines. Methods: For this purpose, CD4⁺CD25⁻ or CD4⁺CD25⁺ T cells from donors allergic to grass or birch pollen (mainly with rhinitis) or from healthy nonatopic donors were stimulated in the presence of autologous, mature, monocyte-derived, allergen-pulsed dendritic cells, and the preactivated CD4⁺CD25⁺ T cells were added to CD4⁺CD25⁻ T cells during restimulation. Results: CD4⁺CD25⁺ T cells from the nonatopic donors and from the majority of the patients investigated proliferated poorly, produced fewer cytokines, and inhibited the proliferation and T_H1 (IFN-γ) and T_H2 (IL-4 and IL-5) cytokine production of CD4⁺CD25⁻ T cells but not IL-10 production. The suppression of CD4⁺CD25⁻ T cells by CD4⁺CD25⁺ T cells was at least partially antigen unspecific and not reversible with anti-IL-10, anti-transforming growth factor β, or anti-cytotoxic T lymphocyte–associated antigen 4 mAb but was reversible with IL-2. In some atopic patients preactivated CD4⁺CD25⁺ T cells reproducibly showed strong proliferative responses, produced higher amounts of IL-4 and IL-10 than CD4⁺CD25⁻ T cells, and suppressed only the IFN-γ production of CD4⁺CD25⁻ T cells. Conclusion: These data indicate that regulatory CD4⁺CD25⁺ T cells are present and functional in most atopic patients with allergic rhinitis and are able to inhibit T_H1, as well as T_H2, cytokine production.