Intravenous cyclophosphamide is widely used to treat severe lupus nephritis. Yet interpretation of the literature is limited by the small number of patients evaluated with varied renal histology. We analyzed the renal outcome of cyclophosphamide therapy for diffuse proliferative lupus glomerulonephritis in a cohort of 89 patients from the Glomerular Disease Collaborative Network. Statistical analysis included Wilcoxon rank sum tests or continuity-adjusted chi-square for comparisons between groups. Kaplan-Meier survival function estimates were calculated for renal survival curves. Cox's proportional hazards models were employed for multivariate evaluation. The renal survival rate declined yearly from 89%, to 86%, 81%, 75%, and 71% at year 5. Renal survival was significantly worse in blacks compared with white patients. Among white patients 95% retained renal function at year 5 whereas black patients showed a progressive yearly decline from 85% at year 1, to 79%, 72%, 62%, and 58% at year 5. Racial differences in renal outcome were independent of age, duration of lupus, history of hypertension, hypertension control during therapy, and activity or chronicity indices on renal biopsy. The factors that predispose black patients to more aggressive and treatment-resistant lupus nephritis are not apparent.