The possible direct effect of gonadotrophin-releasing hormone (GnRH) and GnRH agonist (GnRH-A; buserelin) on basal and human chorionic gonadotrophin (HCG)-stimulated progesterone (P) and cyclic AMP (cAMP) production by cultured human luteal cells was examined. Luteal cells from the early or mid-luteal phase were incubated in long-term cultures. They responded to HCG stimulation with a 2- to 3-fold increase in P production and a 2-fold increase in cAMP production. The addition of GnRH (10(-7) and 10(-5) M) or GnRH-A (10(-7) and 10(-5) M) to the medium had no effect on either basal or HCG-stimulated secretion. These results indicate that both GnRH and GnRH-A have no direct effect on human luteal steroidogenesis in vitro.