In view of the temporal relation between elevated concentrations of glucocorticoids and prostaglandins (PG) at the time of parturition, we have examined the effects of dexamethasone on PGE2 output by mixed cell preparations from human placentae at term maintained in short-term (48 or 96 h) culture. Dexamethasone inhibited placental PGE2 output in a dose-dependent fashion. The effect on placental cells was more marked than on short-term cultures of amnion cells and was not influenced by the presence of progesterone. Dexamethasone also inhibited stimulated PGE2 output after addition of arachi-donic acid. These results suggest that glucocorticoids inhibit placental PG output by a mechanism involving attenuation of PG synthase activity or expression and do not support a direct causal role for elevated maternal or fetal glucocorticoids at term on increased placental PG biosynthesis.