In normal pregnancy trophoblast invades the spiral arteries and produces the physiological fibrinoid degeneration of the vessel wall. In pre-eclampsia, physiological change is restricted and pathological change develops in the non-invaded arteries, including acute atherosis. This study was undertaken to determine if lipoprotein(a) [Lp(a)], which is associated with atherogenesis is present in the wall of spiral arteries that have undergone physiological and pathological change. One hundred and sixteen spiral arteries were examined from 18 normal and 24 severe pre-eclamptic pregnancies. Lp(a) was detected in all atherotic and necrotic lesions, in 57% of spiral arteries with medical disorganization or hyperplasia, and in 45% of those with physiological change. When Lp(a) was detected differences were found in the amount seen: it was most in atherosis, less in necrosis, less still in medical change, and least in physiological change. For the same vascular change generally more Lp(a) was detected in the pre-eclamptic group than in the normal group. The detection of Lp(a) helps to distinguish physiological fibrinoid from atherotic and necrotic fibrinoid. Many atherotic and necrotic areas initially overlooked using standard histology were highlighted using immunohistochemistry. Atherosis can develop in spiral arteries that have been invaded by trophoblast. In those with pre-eclampsia, atherosis was found in 56% of decidual but only in 8% of myometrial spiral arteries. Small areas of necrosis were common in physiologically changed arteries from normal pregnancies.