We have examined the ability of activators of adenylate cyclase and cyclic adenosine monophosphate to affect the output of prostaglandins E and F by dispersed cells of amnion and decidua collected from women following spontaneous labor. Cyclic adenosine monophosphate production by amnion and decidua cells was stimulated in a dose-dependent fashion by cholera toxin and by forskolin in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine. Forskolin and cholera toxin also stimulated prostaglandin E and F output from amnion and decidua cells. Similar effects were seen with cells incubated with dibutyryl cyclic adenosine monophosphate +/- 3-isobutyl-1-methyl xanthine. The beta-adrenergic receptor agonists salbutamol, isoproterenol, and epinephrine all stimulated prostaglandin E and F output from dispersed cells of both tissues. The stimulatory effect of 3-isobutyl-1-methyl xanthine was partially additive with the Ca2+ ionophore A23187. Basal outputs of prostaglandin and outputs stimulated by A23187 and by N6, O2'-dibutyryl adenosine 3':5'-cyclic monophosphate were attenuated by the calmodulin antagonist trifluoperazine in a dose-dependent fashion. We conclude that mechanisms exist for stimulation of adenylate cyclase in human amnion and decidua resulting in enhanced prostaglandin output. This pathway requires basal interaction with Ca2+-calmodulin and may be additive with cyclic adenosine monophosphate-independent mechanisms for prostaglandin stimulation.