This study was designed to determine whether allergen-specific T cells from patients with mild atopic disease were similar to TH2 cells. Tetanus-specific and house mite-specific T-cell clones were derived from peripheral blood of donors with strong immediate epicutaneous skin tests to Dermatophagoides farinae but with mild allergic disease. Overall, the tetanus- and mite-specific clones produced similar amounts of interleukin-4 (IL-4) and gamma interferon (INF-gamma). However, when donors were divided into those with high and low serum levels of mite-specific IgE as determined by RAST, mite-specific clones from donors with high specific IgE produced significantly more IL-4 and less IFN-gamma than mite-specific clones from donors with low levels of specific IgE. These results suggest that circulating allergen-specific T cells from patients who do not have severe allergic disease may nonetheless be skewed toward a TH2 profile. We also examined IL-4 and IFN-gamma production during primary culture of antigen-stimulated peripheral blood mononuclear cells. Detectable amounts of IL-4 were not produced. Stimulation with tetanus antigen induced two to three times as much IFN-gamma as did stimulation with mite antigen. However, the amount of IFN-gamma produced during primary culture did not correlate with the cytokine production of the T-cell clones subsequently generated.