Soluble interleukin-2 receptor (IL-2R) levels were measured and correlated prospectively with clinical, histologic and serologic findings over a 9-month period in 62 lupus patients. Initially, 39 patients had clinical nephritis and 23 patients did not have nephritis. The 62 lupus patients has significantly higher IL-2R than 15 normal controls, most of this difference attributable to patients with nephritis. During lupus nephritis flare 9 of 10 patients showed significant elevations of IL-2R while only 6 of the 10 patients showed either elevation of anti-DNA antibody or decrease in CH50. During disease remission or stable clinical activity changes in IL-2R levels paralleled changes in anti-DNA antibody and CH50. Nephritis patients with cellular proliferative histology had significantly higher IL-2R levels than those with membranous or mesangial nephropathy. IL-2R correlated strongly with histologic activity and chronicity indices, IgG and C3 deposition whereas anti-DNA antibody and CH50 levels did not. IL-2R levels did not correlate with serum creatinine suggesting that elevations of IL-2R were not simply due to decreased clearance. These observations suggest that serum IL-2R level is a useful marker of disease activity in lupus nephritis and may serve as a helpful adjunct in management of this disorder.