We studied levels of soluble interleukin-2 receptors (IL-2R), which are released by activated lymphocytes, in 139 serum samples from 12 patients with systemic lupus erythematosus (SLE). Concentrations of soluble IL-2R were significantly increased in SLE patients compared with controls (P less than 0.001), and they were significantly higher in patients during active SLE defined by low C3 levels (P less than 0.001), low C4 levels (P less than 0.001), or proteinuria (P less than 0.05) than during inactive SLE. Elevated levels of soluble IL-2R correlated with hypocomplementemia in longitudinal studies (P less than 0.001). Measurement of serum concentrations of soluble IL-2R may provide a sensitive and specific method for monitoring disease activity and immune activation in patients with SLE.