To determine whether enhanced matrix synthesis by systemic sclerosis (SSc) fibroblasts in vitro is due to increased responsiveness to transforming growth factor-beta (TGF-beta), fibronectin release by SSc and normal fibroblasts (7 pairs) was measured at various concentrations of TGF-beta. In the absence of TGF-beta, SSc fibroblasts released 30+/-22% more fibronectin than normal fibroblasts. While both SSc and normal fibroblasts increased fibronectin release at all concentrations of TGF-beta tested, the percentage increases were not statistically greater for the SSc fibroblasts even though 4 of the SSc fibroblasts strains were selectively sensitive to low concentrations of TGF-beta. TGF-beta increased cell numbers of both SSc and normal strains equally. Our data confirm abnormal regulation of fibronectin gene expression in SSc fibroblasts and suggest increased sensitivity to TGF-beta by some SSc fibroblast strains.