Reports have so far accumulated suggesting that cyclic nucleotide may play an important role in the regulation of placental function, including fetal growth. However, only biochemical data are available on the localization of adenylate cyclase (AC) and guanylate cyclase (GC) and direct histochemical evidence is lacking. Therefore, to understand the cyclic nucleotide metabolism in human term placenta, ultracytochemical localization of AC and GC activity was studied. The AC activity was mainly positive on the basal plasma membrane of syncytiotrophoblast and on the pinocytotic vesicle of fetal capillary endothelial cell. GC activity was observed to be strong on the plasma membrane of microvilli of syncytiotrophoblast. All the cytochemical control studies confirmed the specificities of each enzyme activity. These observations suggest that syncytiotrophoblast may play an important role in cyclic nucleotide metabolism and that AC may receive information from fetal circulation, whereas GC may receive regulation from maternal circulation.