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We assessed renal histological features in 20 children with diffuse proliferative lupus nephritis (DPLN) to determine whether they were useful in predicting clinical outcome. Renal biopsies were analyzed by assigning scores indicating an activity index (AI) and chronicity index (CI). Clinical assessment of renal function at biopsy and outcome were graded according to urinalysis, serum creatinine, need for dialysis and/or transplantation, and/or death from end-stage renal failure. Renal function at biopsy correlated significantly with AI and CI. Serum complement (C3 and C4) correlated significantly with CI but not with AI. The usefulness of the clinical grading system was confirmed in ten patients who underwent repeat biopsies. Of these, four converted from DPLN to mesangial or membranous lupus and showed improvement in their grade, while only one of the six with DPLN on both biopsies improved. After a mean follow-up of 4.0 years, 14 of the 20 patients showed clinical improvement, four were unchanged, and two were worse. CI predicted clinical outcome (P less than 0.01) but AI did not. Histologic scores of AI and CI obtained from renal biopsies showing DPLN may be useful in predicting therapeutic responses and designing prospective clinical trials to determine optimum management of children with DPLN.