Existence of secretory granules and exocytosis during secretion of human chorionic gonadotropin (hCG) in human placenta has been a point of controversy. Using two methods, the highly sensitive avidin-biotin complex (ABC) method and the protein A-gold technique, for immunochemical identification of beta-hCG on electron microscopic sections, we have examined placentas at 8-10 weeks gestation and at term for the presence of secretory granules. First-trimester placentas demonstrated plentiful syncytiotrophoblast cytoplasmic granules, some undergoing exocytosis, when stained using specific beta-hCG antiserum in the ABC and protein A-gold methods. Term placentas did not show positive reaction product. The data demonstrate that the classic secretory granule-exocytosis pathway mediates placental hCG secretion. However, clear morphological differences exist between placenta granules and hormone secretory granules observed in pituitary, consistent with known functional differences between these organs. This methodology will be useful for further studies of the secretory pathways for placental peptides.