IgE synthesis is controlled by interleukin (IL)-4 and interferon (IFN)-γ, but there is heterogeneity in the IL-4 response depending on the sensitization of patients and natural allergen exposure. In patients sensitized to various allergens, we studied the synthesis of IL-4, IFN-γ, and IgE to determine to what extent their in vitro immune response may be influenced by pollen season, depending on their sensitization. We studied 12 nonallergic individuals, seven patients sensitized to cypress pollen, 12 sensitized to grass pollen, 14 sensitized to several pollens, and 42 patients with polysensitization. The release of IL-4 and IFN-γ from peripheral blood mononuclear cells stimulated by polyclonal agents (calcium ionophore A23187 and phorbol myristate acetate) was measured by ELISA. The spontaneous and IL-4-induced release of IgE was measured by ELISA. In patients with cypress pollen allergy, IL-4 and IgE release were significantly lower than in patients with other allergies. In the pollen-sensitized group, IL-4 and IgE release were significantly higher during the pollen season than out of it. No variation in IL-4 or IgE release was observed in the polysensitized group. IFN-γ production was not affected by the pollen season. These data show that the seasonal variations of IL-4 and IgE synthesis differ according to the sensitization of patients. (J ALLERGY CLIN IMMUNOL 1995;96:932-40.)