To determine the natural history in early immunoglobulin A (IgA) nephropathy, we evaluated the long-term follow-up of 27 normotensive nonazotemic adult idiopathic IgA nephropathy patients with chronic hematuria who derived from a prospective regional epidemiological study of glomerulonephritis conducted between 1978 and 1984. As controls, 17 thin glomerular basement membrane (GBM) patients, 24 patients with normal renal tissue, and nine patients with miscellaneous nephropathies were followed up. Median follow-up was 11 years (range, 8 to 14 years). Renal biopsies, performed within 2 years after patient identification, were scored semiquantitatively in terms of activity and chronicity indices, using a modified National Institutes of Health (NIH) scoring system. During follow-up, two patients with IgA nephropathy went into histological remission, and 12 IgA nephropathy patients showed disease progression, of whom three developed renal failure. Initial proteinuria over 1 g/d was associated with a high activity score, extracapillary lesions, and late onset of uremia. Mesangial IgG deposition and a higher initial chronicity index were associated with development of hypertension during follow-up. In the multivariate analysis, a high initial chronicity index, erythrocyturia, and mesangial IgG deposition are independent determinants of progression of disease. We conclude that in patients with IgA nephropathy, identified early in the course of disease, erythrocyturia, a high chronicity index, and mesangial IgG deposition in the presence of normal renal function are risk factors for decreased renal survival. Disappearance of hematuria is associated with remission of IgA nephropathy immunopathologically and low activity and chronicity indices at initial biopsy.