Between 1980 and 1994, 38 children with severe forms of Schönlein-Henoch purpura glomerulonephritis were entered into a prospective study to evaluate methylprednisolone pulse therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and/or had 50% or more crescentic glomeruli. Initial renal biopsies were obtained from all patients and revealed diffuse proliferative endocapillary glomerulonephritis in 2, focal and segmental glomerulonephritis in 4, and endo- and extracapillary glomerulonephritis in 32, 21 of whom had 50% or more glomeruli with crescents. Patients were treated with intravenous pulse methylprednisolone (3 days) followed by oral prednisone (3.5 months). At the latest follow-up, 1-16 years after initiation of therapy, 27 children had clinically recovered, 3 showed minimal urinary abnormalities, 4 persistent nephropathy, and 4 had progressed to end-stage renal failure. Sequential renal biopsies were obtained from 30 patients, 7-25 months after initiation of therapy. The clinical outcome correlated well with of the activity (hypercellularity, cellular and fibrocellular crescents, and interstitial edema with mononuclear cell infiltrates) and the chronicity (fibrous crescents, glomerular sclerosis, tubular atrophy, and interstitial fibrosis) indexes of post-therapy biopsies. Of particular interest were the post-therapy biopsies of the 18 patients who clinically recovered. They showed a significant decrease of the activity index from 5.1+/-1.1 to 0.4+/-0.8 with a decrease or even a disappearance of IgA deposits, while the chronicity index remained low (0.4+/-0.8 compared with 1.4+/-1). Although uncontrolled, our study suggests that methylprednisolone pulse therapy is effective in those patients at risk of progression of their nephropathy, especially if started early during the course of the disease before the crescents become fibrous.