Fourteen patients with severe systemic lupus erythematosus and nephritis were treated with high-dose intravenous methylprednisolone (IVMP) pulse therapy. Six patients (group 1) received one or two courses of 1 gm of IVMP when they were acutely ill with rapidly progressive renal failure or with multisystemic disease. All patients had a poor outcome; three died and three had end-stage renal disease. Eight patients (group 2) were treated with repeated pulses of 1 gm of IVMP for four to 21 months. Six of the eight patients had a favorable outcome, with four in complete remission and two in partial remission. One of the eight patients had partial response with stable renal disease at 16 months after pulse therapy. Only one patient had no response, with gradual worsening of renal function. All patients in both groups had rapid improvement of levels of anti-DNA and CH50 after pulse therapy was started. Patients in group 2 were compared to 21 randomized patients (group 3) with comparable severity of disease. Renal function deteriorated in group 3, with a mean duration of disease of 82.5 +/- 56.4 months. Renal function improved in group 2, with a mean duration of disease of 87.8 +/- 46.8 months. We conclude that repeated monthly pulse therapy with IVMP in severe SLE was effective and that major side effects can be avoided with proper timing of pulsing.