Human umbilical vessels are devoid of nerves and therefore endothelial cells may play an important role in the control of fetoplacental blood flow. In this study we examined the pharmacological effects of various substances, known to produce endothelial-mediated vasodilation in many blood vessels, on the human umbilical artery and vein from legal terminations [mean gestational age, 15 (8-17) weeks; n = 12] and normal term vaginal deliveries [mean gestational age, 39 (38-41) weeks; n = 12]. Acetylcholine, adenosine 5'-triphosphate, the calcium ionophore A23187 and substance P had no effect on raised vascular tone, whereas sodium nitroprusside relaxed 5-hydroxytryptamine (5-HT) preconstricted, umbilical artery and vein from both early and late pregnancy. L-NG-Nitroarginine methyl ester (L-NAME) had no effect on basal tone or on high tone, after it was raised by 5-HT. Localization of nitric oxide synthase [NOS, type I (neuronal)] was examined in the same umbilical vessels using electron immunocytochemistry. No NOS-immunoreactive endothelial cells were observed in the umbilical vessels taken during early pregnancy. However, the percentage of NOS-immunoreactive endothelial cells in umbilical artery and vein from late pregnancy was 3 and 10 per cent, respectively. These results suggest that nitric oxide contributes little, if any, to the local control of umbilical blood flow throughout pregnancy, despite the presence of NOS-immunoreactivity in a subpopulation of endothelial cells in late pregnancy.