Adenylyl cyclase activity was studied in human endometrium during the menstrual cycle and in human decidua during pregnancy. Higher adenylyl cyclase activity was found in the endometrium than in the myometrium, corpus luteum or Fallopian tubes. In the endometrium, the basal and stimulated activities were highest in the fundus and decreased slightly from the fundus to the isthmus. Prostaglandin-stimulated adenylyl cyclase activity increased gradually from the proliferative phase to the secretory phase, and then quickly reached its highest value in the late secretory phase. Catecholamine-stimulated adenylyl cyclase activity reached a peak in the late proliferative phase and decreased significantly thereafter. Forskolin-stimulated activity was significantly higher throughout the secretory phase than in the proliferative phase. In the decidua, prostaglandin-, catecholamine- and forskolin-stimulated adenylyl cyclase activities in late pregnancy were significantly lower than those in early pregnancy. Our results demonstrate dramatic alterations in adenylyl cyclase activity in human endometrium during the menstrual cycle and in human decidua during pregnancy.