We have studied the distribution of the endothelial isoform of nitric oxide synthase (NOS) through the term human umbilical cord and placenta by immunohistochemistry. Histochemistry with the NADPH diaphorase substrate nitroblue tetrazolium (NBT) has also been used to establish if other isoforms of NOS may be present in these tissues. Positive immunofluorescence for endothelial NOS was found in umbilical cord artery and vein endothelium, although positive staining was only found in approximately 50% of veins. The endothelium of stem villous vessels dissected from beneath the chorionic plate was also intensely immunostained. In the terminal villi punctate immunostaining was found at the basal aspect and around nuclei of syncytiotrophoblast, but was absent from strom and endothelium of terminal villous vessels. A positive histochemical stain for NBT was found in cord artery and vein endothelium and stem villous vessel endothelium. Intense diffuse staining with NBT was found in syncytiotrophoblast, but no other cell types in the terminal villi stained with NBT. The endothelial NOS isoform appears to be localized in the resistance vasculature of the placenta, but not in the capillary endothelium of terminal villi where there is no underlying smooth muscle. It may contribute to the ‘endothelial’ function of syncytiotrophoblast if secreted towards the intervillous space or alternatively fulfil other signal transduction roles. The pattern of staining with NBT was similar to that with endothelial NOS and suggests that other isoforms of NOS are not present in the placental unit. © 1993, Baillière Tindall. All rights reserved.