Latent transforming growth factor-beta 1 (TGF-beta 1) and its binding protein-1 (LTBP-1) are components of the extracellular matrix microfibrils of cultured human fibroblasts. Using immunohistochemistry we have studied the localization of TGF-beta 1 and LTBP-1 and compared their distribution with that of elastic fibres in the interstitial connective tissue matrix of the human dermis. Prominent LTBP-1 specific fibrillar staining co-localized with the elastic fibres in normal human skin. Co-distribution was also observed in a number of pathological states of the elastic fibres such as solar elastosis, solar keratosis and pseudoxanthoma elasticum. TGF-beta 1 had a staining pattern similar to that of LTBP-1 in solar elastosis and solar keratosis. No staining for LTBP-1 or TGF-beta 1 was found in dermis devoid of elastic fibres, as in anetoderma. LTBP-1 is released from the extracellular matrix of cultured human fibroblasts, epithelial and endothelial cells by proteases. Analogously, the immunoreactivity for LTBP-1 and TGF-beta 1 were also lost from the skin sections by elastase, and by trypsin, a protease pretreatment commonly used in immunohistochemistry. These results indicate that LTBP-1 is a component of the elastin-associated microfibrils of the interstitial connective tissue matrix of human skin. Furthermore, the small latent form of TGF-beta 1 is likely to associate with the extracellular matrix of human dermis via LTBP-1. The release of latent TGF-beta 1 from the matrix, as a consequence of proteolytic cleavage of LTBP-1, is a plausible extracellular mechanism for the regulation of TGF-beta 1 activation.