In mammals, transforming growth factor-beta (TGF-beta) is found in 3 highly homologous isoforms that exert their effects via heteromeric complexes of type-I and type-II receptors (TbetaR-I and TbetaR-II). TGF-beta regulates the growth and metabolism of various cell types, including keratinocytes. We have investigated the immunohistological localization of TGF-beta1, TGF-beta2, TbetaR-I and TbetaR-II in normal human skin, basal-cell carcinoma (BCC), Bowen's disease, seborrheic keratosis, eccrine poroma and eccrine spiradenoma using frozen tissue specimens. In normal human skin, the immunoreactive TGF-beta2, but not TGF-beta1, was detected predominantly in the epidermis, follicles and sebaceous glands. The epidermal expression of TbetaR-I and TbetaR-II was very weak in the majority of normal skins. In BCC, TGF-beta2 expression was markedly reduced or completely negative. In addition, TbetaR-I- and TbetaR-II-positive stromal cells were accumulated in the fibrotic stroma in some BCCs. These stromal cells were partly but moderately positive for TGF-beta1. Decreased expression of TGF-beta2 was likely to be associated with the differentiation state of BCC cells, since TGF-beta2 expression was clearly observed in the squamoid foci of BCC. In addition, no expression of TGF-beta2 was detected in the eccrine secretory portion or in eccrine spiradenoma, but it was detected in the upper eccrine ducts and in eccrine poroma.