The short-term prognosis of the "typical", "post-enteropathic" form of infantile HUS is usually good, with a complete recovery of renal function. However, the extent of the renal damage observed on some biopsies may raise concern for the long-term prognosis. Therefore, we studied the outcome of 29 patients affected with classical HUS in infancy or early childhood and followed-up for 15-28 years (m = 18 yrs). Initial renal symptoms ranged from a moderate renal failure with normal diuresis to a 12-day anuria: 21 children had to be treated by peritoneal dialysis. Twenty-five patients underwent a renal biopsy shortly after recovery: lesions of glomerular thrombotic microangiopathy (TMA) were found in 14 patients, and patchy cortical necrosis was diagnosed in the other 11. At latest examination 10 patients had no renal abnormality, 12 had residual renal symptoms (hypertension in 7, proteinuria in 4 and midly reduced GFR in 1), 3 were in chronic renal failure (CRF), and 4 had reached end-stage renal failure (ESRF) 16-24 years after onset; 2 of these latter 4 had a normal GFR at 10-year examination. The long-term evolution was not correlated with the initial clinical severity but appeared well correlated with the extent of the histological damage: 10 of the 11 patients with cortical necrosis have either ESRF (4), CRF (3) or renal sequelae (3), and 4 of the 5 patients with TMA involving more than 50% of glomeruli present with moderate sequelae, whereas the 9 patients with TMA involving less than 50% of glomeruli are symptom-free or have mild sequelae. Thus, the risk of renal failure 20 years after a seemingly cured childhood HUS is not negligible, and renal histology is the best indicator of long-term prognosis.