The present study evaluated the possible effect and mechanism of action of interleukin-1 beta in regulating the release of corticotropin-releasing factor and adrenocorticotropin hormone from human cultured placental cells. With the use of a primary monolayer culture of human placental cells at term, the addition of interleukin-1 beta increased the release of immunoreactive corticotropin-releasing factor with a dose- and time-dependent effect. The intracellular concentration of both cyclic adenosine monophosphate and cyclic guanosine monophosphate increased in the presence of interleukin-1 beta. The addition of indomethacin, a prostaglandin synthesis inhibitor, partially reversed the effect of interleukin-1 beta. The same doses of interleukin-1 beta stimulated the release of adrenocorticotropin hormone and this effect was partially reversed by the addition of a synthetic corticotropin-releasing factor antagonist or by indomethacin. This study showed that interleukin-1 beta increases the release of corticotropin-releasing factor and adrenocorticotropin hormone from cultured placental cells. This effect is associated with increased intracellular cyclic nucleotide concentrations and is in part reversed by a prostaglandin synthesis inhibitor.