The purpose of this study was to assess long-term preservation of renal function in 111 patients with systemic lupus erythematosus and active glomerulonephritis who participated in a randomized treatment trial. Four different drug treatment programs, each of which allowed the use of low-dose oral prednisone in addition to the study drug(s), were compared with a regimen consisting solely of high-dose oral prednisone. Patients randomized to receive intravenous cyclophosphamide, oral cyclophosphamide, or oral azathioprine plus cyclophosphamide had significantly better preservation of renal function than did patients who were randomized to receive prednisone only. Results in the azathioprine group did not differ from those in the prednisone-only group. Cyclophosphamide appears to have long-term benefit in the delay or prevention of end-stage renal disease in patients with lupus nephritis.