OBJECTIVE: Our objective was to determine whether the observed relaxation to lactate and other agents in placental vessels of normal pregnancies is altered in severe preeclampsia. STUDY DESIGN: Isolated placental arteries and veins from women with severe preeclampsia and uncomplicated term pregnancies were precontracted with prostaglandin F-2 alpha under 5% oxygen and 5% carbon dioxide with the balance nitrogen (Po-2 35 to 38 torr) and then exposed to lactate (1 to 10 mmol/L, pH 7.4, n = 8 to 15), arachidonic acid (0.01 to 10 mu mol/L, n = 6 to 13), nitroglycerin (1 nmol to 1 mu mol/L, n = 4 to 12), or forskolin (0.01 to 10 mu mol/L, n = 6 to 9). The response to lactate was also examined in placental vessels from appropriate-for-gestational-age preterm deliveries (n = 8) for comparison with a similar group with severe preeclampsia (n = 8). The t test and analysis of variance statistics were used. RESULTS: Relaxation to lactate was markedly inhibited in both placental arteries and veins of women with severe preeclampsia compared with vessels from uncomplicated term or preterm pregnancies. Responses to the other relaxing agents were not altered in the severely preeclamptic vessels. CONCLUSIONS: In severe preeclampsia absence of lactate-induced dilatation of placental vessels may contribute to the fetal complications associated with impaired blood flow and vasospasm.