Plasma levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked immunosorbent assay in 79 patients with systemic sclerosis (SSc). These levels were significantly elevated in SSc patients, compared with normal controls (mean +/- SEM 866.0 +/- 63.6 units/ml versus 293.0 +/- 20.5; P less than 0.001). Soluble IL-2R levels were highest in patients with generalized disease, were strongly associated with mortality (P less than 0.001) and inversely correlated with disease duration (P = 0.003), but were not related to sex, age, specific visceral involvement, serologic status, peripheral lymphocyte count, or therapy. Levels of sIL-2R in the supernatants of peripheral blood mononuclear cells were low in patients and controls, and showed comparable increases following phytohemagglutinin stimulation. Exposure of peripheral blood mononuclear cells to laminin did not induce sIL-2R release. Circulating IL-2 levels were comparably low in patients and controls. Our findings suggest the presence of lymphocyte activation in SSc, and further suggest that measurement of sIL-2R may prove to be a useful laboratory technique for assessing disease activity.