Transforming growth factor-beta (TGF-beta) has been found in all cells examined thus far, and has been shown to play an important role in inflammation and connective tissue formation. We now report that TGF-beta, alone or in combination with epidermal growth factor (EGF), led to a preferential increase in glycosaminoglycan synthesis by cultures of dermal fibroblasts from patients with progressive systemic sclerosis (PSS) when compared with normal fibroblasts (p less than 0.001). Transforming growth factor-beta increased collagen synthesis to the same extent in both PSS and normal fibroblasts, whereas EGF had no stimulatory activity on collagen synthesis. The addition of EGF to cultures incubated with TGF-beta led to a decrease in collagen synthesis compared with the effect seen with TGF-beta alone (p less than 0.02). These studies suggest that TGF-beta may play an important role in the accumulation of connective tissue seen in PSS and that the combined action of multiple growth factors may modulate the synthetic activity of human dermal fibroblasts.