It is becoming accepted that the haemolytic uraemic syndrome(HUS), thrombotic thrombocytopenic purpura, and related disorders are made up of different diseases that need to be re-classified according to aetiology, pathogenesis, prognosis, and response to treatment. The most prevalent of these disorders follows infection by Escherichia coli that produce verocytotoxin (shiga-like toxin)(VTEC). There is a close correlation between VTEC infection and presentation with diarrhoea. In endemic areas such as the Americas and Western Europe more than 90% of childhood cases of HUS present in this way. This disease is self-limiting and non-recurring, hypertension is transient, and the mortality among childhood cases in the UK is now less than 3% with supportive management only. This pattern contrasts with nondiarrhoeal, non-VTEC cases, which are rare, sometimes familial, and generally have a poor outlook. 1 Among the latter is a newly emerging subgroup of the syndrome with primary abnormalities in the complement regulator factor H or its gene. 2–8 Factor H has a central role in the regulation of complement (figure). 9 Produced mainly in the liver as a single peptide glycoprotein, it circulates in plasma at a concentration of 50 mg/dL. The molecule is made up entirely of 20 folded globular domains known as complement-control-protein modules or short consensus repeats (SCR). Each has its own exon except for SCR 2, which has two. The tertiary structure of the molecule, bent back on itself like the Greek letter α, leaves the C-terminal SCR 20 exposed, which suggests an important role for this site. 9–11 Factor H contains three binding sites for heparin and other polyanions by which it can attach to sialic acid on cell surfaces. One of these binding sites is located in SCR 20. When arrayed on the surface of host cells, factor H is strategically placed to regulate the early events in complement activation and prevent bystander injury. It