Fibroblasts were cultured from affected and unaffected skin sites of 6 patients with localized scleroderma. As a parameter of fibroblast activation, collagen synthesis and cellular pro alpha 1(I)collagen mRNA levels were measured. Cell surface glycoproteins were labelled with the periodate/borohydride method and fractionated electrophoretically. A distinct reduction in the relative amount of surface glycoproteins in the 120 kDa region was observed in two affected cell lines producing increased amounts of collagen and in one affected cell line with normal collagen production when compared to unaffected fibroblast lines. Other, non-systematic alterations in the surface glycoproteins of the affected cell lines were also detected. Compared to unaffected and healthy control fibroblasts no alterations in the surface protein profiles were seen in the other three affected cell lines. These cells did not show an increase in collagen production either. The results suggest that the activation of collagen synthesis found in scleroderma fibroblasts might be connected with alterations in the normal cell surface glycoprotein pattern.