Forty-four patients with systemic sclerosis and 3 patients with localized scleroderma were investigated for plasma endothelin and aminoterminal propeptide of type III procollagen (PIIINP). Although there was an overlap between plasma levels of endothelin in patients with systemic sclerosis and healthy controls, the mean value of the patients was significantly higher than in controls. Plasma endothelin was normal in all 3 patients with localized scleroderma. The highest levels of plasma endothelin were found in patients with type II and III systemic sclerosis with the largest cutaneous involvement, and in patients with the scleroderma-specific antibodies Scl-70 and anticentromere antibodies. Extremely high values were found in a patient who experienced a renal crisis and in a patient who had her lower leg amputated due to severe vasculitis. A positive correlation was found between plasma endothelin and serum PIIINP. This, together with the fact that in systemic sclerosis the vascular lesions are the earliest, would seem to support the theory that endothelial cell damage could lead to increased secretion of endothelin and subsequent fibrosis in this disease.