Lymphokine secretion profiles were studied of human allergen-specific CD4+ T lymphocyte clones (TLC). To this aim, panels of house dust mite Dermatophagoides pteronyssinus (Dp)-specific TLC were generated from two atopic Dp-allergic patients, suffering from severe atopic dermatitis (AD1) and allergic asthma (AD2), respectively, and from a non-atopic individual (NAD). From AD1 additional TLC were cloned specific for tetanus toxoid or Candida albicans, both Ag that were not relevant for the atopic state of this patient. Secretion of IL-2, IL-4, and IFN-gamma was determined after specific stimulation of these TLC, using autologous monocytes as APC. With respect to the production of IL-4 and IFN-gamma, clearly distinct profiles were observed. All Dp-specific TLC from both atopic donors produced IL-4 but not IFN-gamma, whereas the Dp-specific TLC from NAD, as well as the tetanus toxoid- and C. albicans-specific TLC from AD1, all produced IFN-gamma but not or small quantities of IL-4. Most TLC from all panels produced IL-2. These lymphokine profiles were consistent for at least 3 days and were neither dependent on the dose of allergen nor on the atopic or nonatopic state of the donor of APC. The functional consequence of these restricted lymphokine profiles was stressed by the observation that, whereas Dp-specific TLC from AD1 and AD2 supported in vitro IgE production, this support could be abrogated by a Dp-specific TLC from NAD. The present results suggest that CD4+ T lymphocytes that produce IL-4, but not IFN-gamma, occur in high frequencies in the allergen-specific T cell repertoires of atopic donors, which may have important implications for the pathomechanism of atopic disease.