To determine guidelines for treatment with high-dose intravenous methylprednisolone in lupus nephritis, we prospectively assessed the response to pulse therapy in 34 patients. In 12 of them, serum creatinine decreased by at least 20 percent within two months of treatment whereas in the remaining 22 there was no such response. Patients who responded were characterized by recent deterioration in function whereas nonresponders had had a more stable antecedent course (p = 0.003). Responders also had more diffuse lesions on renal biopsy (p = 0.028), had higher levels of anti-DNA antibodies (p < 0.05), and tended to have higher tilers of immune complexes and lower total hemolytic complement. High-dose intravenous methylprednisolone therapy may lead to striking improvement in renal function in lupus nephritis, especially in the subset of patients with recent antecedent functional deterioration. This improvement was maintained in 60 percent of the patients who responded for at least six months. © 1981.