IgA nephropathy has a variable course and leads to renal failure in a substantial number of cases. In an attempt to identify prognostic indicators in this disease, we evaluated the clinical and pathologic findings of 20 unselected patients with IgA nephropathy, 13 of whom were followed for 1.5 to 5 years (mean 2.8 years). Biopsy specimens were obtained from all patients and were examined by light and electron microscopy and by immunofluorescence. The activity and severity of the lesions were graded according to a modified classification used by Meadow et al. for the nephropathy associated with Henoch-Schönlein purpura. The results reveal a correlation between the histopathologic grading in the initial biopsy and the clinical outcome: Patients with mild (grade II) or moderate (grade III) lesions had a benign course or showed evidence of active disease without deterioration of renal function, whereas all patients with grade IV or V lesions who were followed for more than one year developed end-stage renal failure. These observations suggest that histologic grading at initial renal biopsy may be a useful prognostic indicator of the clinical outcome of IgA nephropathy.