Background: Allergen-stimulated IL-5 production by CD4+ T cells is the key issue in atopic asthma. On the other hand, virus-specific CD8+ T cells produce IL-5 and might play an important role in the pathogenesis of nonatopic asthma. Objectives: We sought to compare the IL-5-producing T-lymphocyte subsets in the peripheral blood of atopic and nonatopic asthmatic subjects, especially the contribution of IL-5-producing CD8⁺ T cells in nonatopic asthma. Methods: Heparinized blood samples were obtained from subjects with atopic asthma (n = 10), subjects with nonatopic asthma (n = 10), and healthy subjects (n = 10) and stimulated with ionomycin and phorbol myristate acetate in the presence of brefeldin A. Two-color flow cytometric analysis with mAbs to cell-surface antigens and intracellular IL-5 was used to detect the IL-5-producing T-cell subsets. Results: A higher percentage of IL-5-producing CD3⁺ T cells was detected in subjects with atopic and nonatopic asthma than that seen in the healthy subjects. The percentage of IL-5-producing CD4⁺ T cells was significantly higher in subjects with atopic asthma than in the healthy subjects. The percentage of IL-5-producing CD8⁺ T cells was significantly higher in subjects with nonatopic asthma than in the healthy subjects. The percentage of IL-5-producing CD8⁺ T cells was higher in subjects with nonatopic asthma than in those with atopic asthma, but the difference was not statistically significant. Conclusions: CD4⁺ T cells are the major source of IL-5 among CD3⁺ lymphocytes in subjects with atopic asthma. On the other hand, increased IL-5 production by CD8⁺ T cells, as well as by CD4⁺ T cells, is a characteristic feature of nonatopic asthma. (J Allergy Clin Immunol 2002;109:294-8.)