Until recently it was believed that the T cell response of atopic dermatitis patients challenged with inhalant allergens originates almost exclusively and specifically from Th2 cells capable of secreting an abundance of interleukin (IL)-4 while producing no interferon (IFN)-gamma. To reevaluate this concept in a large cohort of atopic dermatitis patients we established 177 CD4+ T cell clones (45 of which showed specificity for house dust mite antigen) from the peripheral blood (n = 76), naturally occurring skin lesions (n = 40), and allergen-exposed skin (n = 61) of different patients. These clones were examined for their capacity to secrete IL-4 and IFN-gamma upon mitogenic stimulation. Moreover, 20 of these T cell clones were investigated for the synthesis of transcripts for IL-5, another Th cytokine. Our results indicate that the majority (52-100%) of allergen-specific T cells in both skin and blood of atopic individuals failed to exhibit a restricted cytokine secretion pattern and thus were classified as Th0 cells. House dust mite antigen specific T cells displaying a restricted secretion pattern (n = 16) were either of the Th1 or the Th2 type. Specific Th2 cells, however, were found almost exclusively in allergen patch test reactions, indicating that the Th2 differentiation pathway is seen preferentially in allergen-exposed skin. The cytokine secretion profile of T cell clones obtained from naturally occurring skin lesions showed similarity to those of patch test lesion, suggesting that the patch test represents a useful model to investigate the pathogenesis of atopic dermatitis.