Activation of the enzyme adenylate cyclase or treatment with dibutyryl cyclic AMP (dbcAMP) stimulates prostaglandin biosynthesis in vitro and in vivo. Prior activation of adenylate cyclase has been shown to inhibit the stimulation of amnion cell prostaglandin E2 (PGE2) biosynthesis by substances such as epidermal growth factor (EGF) and phorbol 12-myristate 13-acetate (PMA). Little is known, however, concerning the effects of activation of the adenylate cyclase system on basal and stimulated prostaglandin biosynthesis in human chorion and decidual cells. Interleukin-1 beta (IL-1 beta), EGF, ionomycin (iono), and PMA are known to stimulate prostaglandin E2 production in human chorion and decidual cells. Hence, we have evaluated the effects of co-treatment of chorion and decidual cells with dbcAMP in the presence and absence of EGF, PMA, IL-1 beta, and iono on prostaglandin production. dbcAMP alone stimulated chorion and decidual PGE2 production. Coincubation of dbcAMP with all four test stimulants resulted in a further enhancement of decidual PGE2 production that was often more than additive. Thus activation of adenylate cyclase can have effects on prostaglandin production that have specificity with respect to tissue source, presence of other stimulants and relative time of exposure of the tissues to each of the substances involved.