Injury to vessel walls, especially microvascular damage due to free radicals, has been a focus of interest concerning the pathogenesis of systemic sclerosis. Excess reactive oxygen species may induce antioxidant defenses. We therefore measured plasma superoxide dismutase (SOD) activity in patients with systemic sclerosis and found average SOD activity of plasma in 16 patients with systemic sclerosis (5.00 +/- 3.10 U/ml) to be significantly (P < 0.001) higher than those in 89 healthy volunteers (1.56 +/- 0.234 U/ml). Patients with Raynaud's phenomenon and/or skin sclerosis had particularly high SOD activity. These findings suggest that plasma SOD activity may serve as a useful parameter for assessment of sclerotic progression and the presence of Raynaud's phenomenon.