Atopy is heterogeneous and the IgE immune response of patients allergic to a single allergen (monosensitized) differs from that of those allergic to multiple allergens (polysensitized). Since interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) regulate human IgE synthesis in vitro, we determined whether cytokines may be involved in the heterogeneity of atopy by comparing the serum IgE and sCD23 titres to the cytokine profile of T lymphocytes from 44 atopic patients (13 mono- and 31 polysensitized) and seven non-atopic subjects. Monosensitized patients were allergic to grass or cypress pollens or house dust mites, and polysensitized ones to many pollen species (n = 5) or many allergens (n = 26). Total serum IgE was lower in the control group than in both atopic groups and in the monosensitized group than in the polysensitized one. IgE immunoblots to orchard grass pollen and house dust mites were less heterogeneous in the monosensitized group than in the polysensitized one. IL-4 production by in vitro-activated peripheral blood mononuclear cells (PBMC) was significantly higher in the polysensitized group than in the monosensitized, and marginal in the control group. In contrast, IFN-gamma production was strongly reduced in both atopic groups, and IL-2 production comparable in the three groups. IgE and soluble CD23 (sCD23) release was higher in the atopic groups than in the control, and higher in the polysensitized group than in the monosensitized one. This study shows that PBMC of mono- and polysensitized subjects have a different IL-4 and sCD23 profile and suggests that human beings may be classified into high and low IgE responders on the basis of IL-4 production.