Pre-eclampsia (PE) is a pregnancy-specific syndrome that is the principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy-associated deaths (American College of Obstetricians and Gynecologists 1996). Hippocrates first described the condition when he wrote in one of his Aphorisms that ‘convulsions take place from either repletion or depletion’ (Salas 1999). Hippocrates had observed the sudden and unexpected appearance of maternal grand-mal seizures, which occur when PE progresses to eclampsia, the word being derived from the Greek for ‘lightning’. It was believed for many centuries that PE was a seizure disorder unique to pregnancy, but during the last 200 years this view of the disease has changed drastically and we now know that it is not only a convulsive disorder. Several new findings have led to this change in opinion. At the turn of the last century, the new ability to measure blood pressure led to demonstration of the association of PE and hypertension (Cook & Briggs 1903); hypertension was often found to precede the development of eclamptic seizures. Young (1927) described placental damage that led to pregnancy-induced toxaemia. Later, the involvement of the kidneys was also observed since women who had died from eclampsia also had a unique form of glomerular endotheliosis (Bell 1932). These findings persuaded many to view the syndrome as a hypertensive rather than a seizure disorder (American College of Obstetricians and Gynecologists 1996). This change in classification unfortunately led many researchers to devote attention to the cause of the hypertension, to the exclusion of other facets of the disease (Roberts & Redman 1993). PE is now unanimously viewed as a multisystem disorder, as increases in blood pressure are rarely responsible for multi-organ dysfunction (Friedman et al. 1991). What is the array of complications associated with PE? In its latest document, the National Institutes of Health (2000) define mild PE as including an increase in blood pressure to greater than 140 mmHg systolic or 90 mmHg diastolic in a woman normotensive before her 20th week of pregnancy. Proteinuria is also present with a urinary excretion of at least 0·3 g protein in a 24 h specimen. Mild PE can develop directly into severe PE over a matter of days or weeks, this advancement being unpredictable in both its onset and its progression. There is a vast diversity of additional symptoms associated with this change (Patrick & Roberts 1999). These can include cerebral oedema (Cunningham & Twickler 2000), neurological manifestations (including headache, confusion, paralysis, coma, visual loss and seizures) (Royburt et al. 1991, Thomas 1998), liver capsule distension (Sheehan & Lynch 1973), renal failure (Lindheimer & Katz 1992), pulmonary oedema (Davison 1997), thrombocytopenia (Pritchard et al. 1987), coagulopathy (Barron et al. 1999), HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome (Weinstein 1982) and nausea (Martin et al. 1999). The primary cause of PE has been difficult to elucidate because its symptoms have always presented as a cluster of conditions. Several theories have been advocated and by far the most compelling evidence indicates that the placenta holds the key. The symptoms of PE disappear soon after birth or after pregnancy termination (Palma Gamiz 1998) when the placenta is no longer present. It is also apparent that the presence of a foetus is not necessary as some cases of hydatidiform mole, in which the uterus contains only disordered placental tissue, are complicated by the condition (Scott 1958). Finally, an utero–placental interaction is not required, as abdominal pregnancies can still encounter complications (Shembrey & Noble 1995). However, as PE affects only 5–10% of first pregnancies the presence of a placenta cannot be the sole cause. What then is different in the placentae of women prone to develop PE? Page (1939) first noted that placentae from these women appeared to be poorly perfused and today we know that a consistent feature associated with this poor perfusion is the defective trophoblast invasion of the myometrial portion of the spiral arteries (Pijnenborg et al. 1980, 1981). In normal pregnancy, trophoblast invasion of the spiral arteries renders them dilated, flaccid and unresponsive to vasoconstrictive agents (Brosens et al. 355