We have established a large panel of T-cell clones (TCCs) specific for Dermatophagoides pteronyssinus and Lolium perenne group I grass pollen allergens (total, 61) and for tetanus toxoid and protein purified derivative bacterial antigens (total, 38) from the peripheral blood of two atopic individuals and then analyzed their ability to produce interleukin 4 (IL-4), IL-5, and interferon gamma (IFN-gamma). Upon stimulation with phorbol 12-myristate 13-acetate plus anti-CD3 antibody, the great majority of TCCs specific for bacterial components was able to produce both IL-4 and IFN-gamma, whereas most D. pteronyssinus- and L. perenne group I-specific TCCs produced IL-4, but no, or limited, IFN-gamma. Moreover, the mean amounts of IL-4 and IFN-gamma released by allergen-specific TCCs were significantly higher and lower, respectively, than the mean amounts produced by TCCs specific for bacterial components. Under the same experimental conditions, virtually all allergen-specific TCCs, but only one-third of tested TCCs specific for bacterial components, expressed IL-5 RNA and secreted IL-5 in their supernatants. Eighteen TCCs (nine specific for allergens and nine specific for bacterial components) were also assessed for their ability to induce IgE synthesis by autologous B cells in response to stimulation with the specific antigen. Under these experimental conditions, all allergen-specific TCCs, but only one-third of TCCs specific for bacterial components that produced IL-4 but no, or little, IFN-gamma induced the synthesis of detectable amounts of IgE. The demonstration that most allergen-specific helper T cells in atopic individuals are able to produce high amounts of IL-4 (and IL-5), but no IFN-gamma, may explain why allergens induce production of IgE antibodies and increase eosinophils.