Interleukin-4 (IL-4) has been demonstrated to induce IgE synthesis by peripheral blood mononuclear cells (PBMNCs) of healthy donors. In this study, we demonstrated that IL-4 also can enhance spontaneous IgE synthesis by PBMNCs of allergic/atopic patients and patients with Buckley's or hyper-IgE syndrome. Spontaneous IgE production by PBMNCs of these patients was suppressed by interferon (IFN)γ or IFN-α in a dose-dependent fashion. Despite high serum IgE levels, no IL-4 could be detected in the serum of the patients, but indirect evidence was obtained indicating that enhanced IL-4 production in vivo may be associated with the high serum-IgE levels in these patients. Spontaneous IL-4 production was measured in PBMNC cultures of 4 21 patients tested. Furthermore, spontaneous IgE synthesis by PBMNCs of three other patients of seven tested in vitro was partly blocked by anti-IL-4 antiserum. In addition, levels of soluble CD23 (which is specifically induced by IL-4) were strongly elevated in sera of patients. Finally, activation of PBMNCs of the patients resulted in levels of IL-4 and of IFN-γ synthesis that were higher and lower, respectively, than levels produced by PBMNCs of healthy-control donors tested in parallel. Collectively, our data indicate that spontaneous IgE synthesis in vitro can be modulated by IL-4, IL-5, IFN-γ, and IFN-α. In addition, our data suggest that enhanced IL-4 and reduced IFN-γ production is associated with the elevated serum IgE levels observed in these patients.