Human corpora lutea (CL) of the menstrual cycle or early pregnancy were excised at operation, cut into pieces, and incubated in the presence of human chorionic gonadotropin or prostaglandin (PG) I2 and D2. After incubation, the tissue levels of 3',5' cyclic adenosine monophosphate (cAMP) and the medium concentration of progesterone (P) was determined. Prostaglandin I2 and PGD2 stimulated cAMP production in the CL of both the menstrual cycle and early pregnancy. This stimulatory effect was maximal for PGI2 after 5 minutes and for PGD2 after 10 minutes. Repeated addition of the PGs during 120 minutes in the CL from the menstrual cycle resulted in a persistent cAMP elevation and stimulated P formation. The stimulatory effects of PGI2 and PGD2 on cAMP and P production in vitro indicate that these local hormones play a role in the normal development of human menstrual CL and in the persistence of the CL of early pregnancy.