A subgroup of patients with hemolytic-uremic syndrome (HUS) has emerged with complement factor H deficiency. These have come to light because of persistent hypocomplementemia, although the molecular finding by Warwicker et al in one pedigree suggests that not all cases exhibit systemic hypocomplementemia. These patients have an atypical presentation in that they do not consistently have a prodrome of enterocolitis although precipitating factors may include infections of various kinds. Patients usually have severe hypertension early in the course of their illness, tend to relapse, and have a poor prognosis. The age of onset varies from neonates to adults. Plasma exchange and replacement with a plasma product containing factor H seem a reasonable option in the absence of better evidence. Kidney transplantation can meet with recurrence of HUS, but the risk of grafting has yet to be established, and a strategy to overcome graft recurrence is needed. Because of the great rarity of this disorder, a strong case can be made for international registries of atypical HUS cases so that clinical and laboratory investigation is promoted.