Background: Although IL-4, IL-13, and IFN-γ are known to affect IgE synthesis, it remains unclear which one plays the most important role in in vivo IgE synthesis in atopic patients. Objective: The aim of this study is to clarify the difference in importance among these cytokines in up-regulation of IgE synthesis in atopic patients. Methods: We measured IL-4, IL-13, and IFN-γ production by PBMCs on stimulation with house dust mite (HDM) in 23 children, 3 to 15 years old, with bronchial asthma (BA) and analyzed the correlation with HDM-specific IgE antibody levels expressed as HDM IgE radioallergosorbent test (RAST) results. Results: The production of IL-4 and IL-13 by PBMCs on stimulation with HDM was significantly higher in children with BA than in nonatopic control subjects (IL-4, 752.9 ± 365.9 vs 312.3 ± 230.0 fg/mL, P < .001; IL-13, 21.9 pg/ml [<12.0-77.6] vs <12.0, P < .01). IL-4 production showed a close positive correlation with HDM IgE RAST (r = 0.71, P < .001), which was distinctly stronger than that between IL-13 production and HDM IgE RAST (r = 0.46, P < .05). IFN-γ production was neither different between children with BA and nonatopic control subjects (7.24 [1.54-33.90] pg/mL vs 11.2 [1.66-75.9] pg/mL) nor correlated with HDM IgE RAST levels. Essentially the same result was obtained by stimulation of PBMCs with a purified HDM major allergen Der f 1. Conclusion: IL-4 is likely to be the most important cytokine in up-regulation of in vivo IgE synthesis against HDM in children with BA. (J Allergy Clin Immunol 2000;105:327-32.)