The immune response to environmental allergens depends on both genetic and environmental factors. Allergen exposure triggers the activation of allergen-specific Th2 cells in allergic patients, as well as increased Th2-type cytokine mRNA expression and eosinophil recruitment. Nevertheless, different patterns of release of cytokines could explain the heterogeneity of atopic response. In our study, 25 patients with pollinosis and 15 healthy donors were selected to characterize their release of Th2 (interleukin [IL]-4 and IL-5) and Thi (interferon-gamma [IFN-y]) cytokines, both during and outside the pollen season. Peripheral blood mononuclear cells from patients and controls were isolated, cultured in the presence of phorbol-12-myristate-13- acetate plus ionomycine, and phytohemagglutinin (PHA), and cytokine release was assessed by titration in the supernatants. Both IL-4 and IL-5 showed higher levels during than outside the pollen season in pollinic patients (P<0.05) after nonspecific stimuli, whereas IFN-y levels were significantly lower during than outside the pollen season only after culture with PHA. Significant differences were not observed in the control group. Our results are consistent with the hypothesis that release of cytokines by peripheral blood mononuclear cells from patients with pollinosis depends on environmental exposure to sensitizing pollens, and that influence can be revealed by in vitro nonspecific stimulation. Nevertheless, the heterogeneity in results suggests that the use of mitogens to assess Thl/Th2 dominance may need careful evaluation.