The present study was undertaken to evaluate the effects of the glucocorticoid hormones betamethasone and hydrocortisone, and of progesterone on the relative production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) by explants of human fetal membranes at term gestation in the absence of labor. Tissues (n = 7) were incubated either in the presence or in the absence of the above mentioned hormones. PGE2 and LTB4 were measured in culture medium by radioimmunoassays. Glucocorticoids and progesterone did not affect PGE2 output by tissues; however, they greatly stimulated LTB4 production. Moreover, both betamethasone and hydrocortisone significantly increased the ratio of LTB4 to PGE2 formation by tissues. These results suggest that glucocorticoid hormones and progesterone might influence arachidonic acid metabolism in human fetal membranes by stimulating the production of lipoxygenase rather than cyclooxygenase substances before the onset of labor.