We investigated the expression of transforming growth factor-beta (TGF-beta) isoforms in involved and uninvolved areas of skin from patients with systemic sclerosis (SSc) and normal controls. Paraffin-embedded skin specimens were stained for TGF-beta 1, TGF-beta 2, and TGF-beta 3 using the avidin-biotin-peroxidase technique. TGF-beta 2 was expressed intensely in the extracellular matrix of the skin biopsies obtained from involved areas of patients with SSc, in contrast to the uninvolved areas and normal individuals. TGF-beta 2 was deposited throughout the entire dermis and also in a linear fashion along the dermoepidermal junction and in the perivascular areas of SSc-involved skin. Although infiltrating mononuclear cells were not present in great numbers, they did not stain for TGF-beta 2. TGF-beta 1 and TGF-beta 3 were not expressed in the extracellular space in either patients or normal controls, except in rare cases. The cellular staining which was observed for all three isoforms did not differ between involved and uninvolved skin and normal controls. The finding of increased deposition of TGF-beta 2 in the involved skin of patients with SSc implies that it may be involved in the pathologic fibrotic process.