Case-control and cohort studies support the hypothesis that postmenopausal oestrogen-replacement therapy reduces the risk of atherosclerotic disease manifestations. The evidence for a cardioprotective effect of such a therapy is, however, incomplete because randomized prospective studies are missing. Because it may be almost impossible to conduct placebo-controlled trials in the future, other study designs will be needed to minimize selection bias. Further work is required to define the optimal dose and administration schedule of oestrogen and to determine whether addition of progestogens alters the beneficial effect of oestrogen on the cardiovascular system. Such studies may also provide mechanistic insight into the interaction between lipoprotein metabolism and haemostasis and its relation to the atherosclerotic disease process.