We measured mitogenic activity of whole blood serum and platelet-poor plasma-derived serum of a group of 10 patients with progressive systemic sclerosis and of 8 controls. Mitogenic activity of plasma-derived serum was greater in patients than in controls, in the absence of other signs of platelet activation. This increased activity was inhibited by specific antibodies, anti-platelet derived growth factor, suggesting that circulating levels of platelet-derived growth factor may be present in progressive systemic sclerosis patients. Platelet-derived growth factor, released either by platelets or by monocytes, might play a role in the pathogenesis of scleroderma.