Clinicopathological data in 74 patients with IgA nephropathy were analyzed with special attention to level of proteinuria and its prognostic significance in this disease. Excretion rates exceeding 3 g per day (heavy), in the range of 1 to 2.9 g (moderate) and under 1 g per day (mild) each occurred in approximately equal proportions of patients. One-sixth of those with more than 1 g developed end-stage renal failure, while serum creatinine never exceeded 2 mg/dl in any with mild proteinuria. "Renal survival" (serum creatinine of 2 mg/dl or less) at five years after presentation was 100% in patients with persistently mild proteinuria, 87% in those whose protein excretion reached the moderate range, and 69% when heavy or nephrotic range proteinuria developed. Of significance, only rarely did mild proteinuria at presentation increase to higher levels. A correlation existed between level of protein excretion and severity of mesangial, segmental or global proliferation, glomerulosclerosis, podocyte effacement, interstitial infiltration, tubular atrophy and vascular sclerosis, even in patients with unimpaired renal function. Moderate or heavy proteinuria typically preceded the onset of hypertension and occurred prior to the development of renal insufficiency. Our results underscore magnitude of proteinuria as an early marker of glomerular damage in the prognosis of IgA nephropathy.