We investigated the prognostic indicators in ten hyperammonemic neonates: four treated by continuous arteriovenous hemodialysis (CAVHD), four with continuous venovenous hemodialysis (CVVHD), and two with hemodialysis (HD). Plasma ammonium levels decreased significantly within the first 24 h irrespective of dialysis modality (from 1419 to 114 micromol/l, median values; P<0.0001). CVVHD achieved the highest ammonium clearance. HD provided highest ammonium extraction but clearance was hampered by severe hemodynamic instability. Five patients had a good outcome (normal at follow-up of 9-59 months), five had poor outcome (four died and one has severe neurological damage). Total coma duration was shorter in patients who had a good outcome (47+/-11 vs 78+/-13 h; P=0.02). Remarkably, only coma duration before dialysis determined this difference (22.2+/-10.1 vs 48.8+/-11.2 h; P=0.02). In cases with good outcome, coma duration was <33 h, whereas the others exceeded this limit. The prognosis was not related to dialysis modality, rapidity in reducing ammonium levels or to the underlying metabolic defect. In conclusion, results showed CVVHD to be the optimal modality for extracorporeal ammonium detoxification. However, the most relevant indicator for prognosis was coma duration before the start of dialysis. Therefore, major efforts should be made to refer patients quickly to highly specialized centers.