To define the CNS manifestations of the hemolytic-uremic syndrome (HUS), the records of 61 consecutive episodes of HUS in 60 patients were reviewed. Major CNS signs (seizures and/or coma) occurred in 30 of the 61 episodes. Twenty-four children had seizures. Analysis of blood pressure and metabolic parameters or admission to the hospital did not predict which child would exhibit CNS signs. However, during the subsequent course of the illness, children with CNS dysfunction had lower minimum serum sodium concentrations and more severe azotemia and were more likely to require dialysis than children without CNS signs. Of the 61 episodes, there were three deaths, and three children suffered major CNS sequelae. Coma at the time of admission and elevated CSF protein levels were features associated with poor outcome.