Background: In view of reports that CD8+ T cells may produce T H2-type cytokines and our own finding that levels of intracellular IL-4 are higher in CD8 than CD4+ T cells in healthy nonatopic subjects, we have hypothesized that the capacity of CD8+ T cells to produce IL-4 may be increased in atopic asthma, a disease characterized by high production of T H2 cytokines. Methods: Levels of IL-4 and interferon-γ were measured by ELISA in cell lysates and in 20- and 48-hour cultures of concanavalin A-stimulated purified peripheral blood CD8+ T cells in seven patients with mild atopic asthma and seven healthy nonatopic subjects. Results: Resting CD8 + T cells in patients with asthma contained significantly more IL-4 than those of healthy nonatopic subjects (median, 26 pg/106 cells; range, 17 to 84 pg/106 cells vs 16 pg/106 cells; 10 to 28 pg/106 cells), with no difference in intracellular interferon-γ levels. In the healthy control subjects, but not in the patients with asthma, levels of intracellular IL-4 correlated negatively with levels of interferon-γ in resting CD8+ T cells (r s = –0.9411, p = 0.005). Stimulation with concanavalin A produced a consistent and significant increase in secretion of interferon-γ, but not IL-4, with no difference between the two groups of subjects. Conclusion: The results of this study suggest that CD8+ T cells from patients with asthma may be an important source of the T H2-type cytokine IL-4. This capacity appears to be acquired in vivo, possibly by conditioning by IL-4 produced in the inflamed airways.