The expression of allergic phenotypes involves complex inter-relationships among several Th2 and Th1 cytokines as well as the regulator cytokine interleukin (IL)-10. These direct or indirect interrelationships may distort the true associations of cytokine responses with these phenotypes. In this study, we aimed to clarify the effects of the regulatory cytokine IL-10 and Th1 cytokine interferon-gamma (IFN-γ) on allergic phenotypes after adjusting for the correlations with Th2 cytokines. After adjusting for Th2 cytokines, IL-10 and IFN-γ were protective against atopy. Adjusted levels of IL-10 and IFN-γ stimulated with house-dust mite (HDM) were significantly lower in atopics than non-atopics, for IL-10 adjusting for IL-5 (P = 0.002), IL-13 (P = 0.012), IL-9 (P = 0.016), and IL-4 (P = 0.043), and for IFN-γ adjusting for IL-5 (P = 0.005), IL-13 (P = 0.005), and IL-9 (P = 0.037). IL-10 and IFN-γ levels stimulated with phytohaemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) exhibited a similar pattern. The adjusted levels of IL-10 and IFN-γ stimulated with HDM, PHA or SEB were all significantly negatively correlated with total serum IgE, except for IFN-γ stimulated with SEB. Levels of Th2 cytokines distort the associations of IL-10 and IFN-γ with allergic phenotypes. Removing the covariance with Th2 cytokines, both IL-10 and IFN-γ were protective against atopy.