We have examined the possibility that corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) might affect prostaglandin (PG) E2 and PGF2α output by term placenta, amnion and decidua during short-term (48-hour) culture, and that effects of CRH might be mediated by ACTH. In all three tissues PG output was stimulated by both CRH and ACTH. These effects were inhibited in the presence of antisera to CRH and to ACTH. Moreover, in placenta, but not in amnion or decidua, the stimulatory effects of CRH on PGE2 and PGF2α output were attenuated in the presence of an antibody to ACTH. Our results support the possibility of paracrine stimulation by CRH and ACTH of PG production in intrautenne tissues, and suggest that in part the effects of CRH on placental PG output might be mediated through ACTH.