The role of prostaglandins (PGs) and leukotrienes (LTs) in the induction of decidualization in the rat uterus was investigated. In the hypophysectomized progesterone (P4) primed rat, intraluminal infusion for four days by osmotic minipump, of PGE2 (1 ug/h), LTC4 (10 ng/h) or 0.15M saline (1 ul/h) significantly elevated uterine weight when compared to the noninfused horn: all were equally effective. In contrast, simultaneous infusion of PGE2 and LTC4 produced an increase in uterine weight which was markedly higher than any other conditions and the reaction was elicited along the entire length of the uterine horn. Infusion of PGE2, LTC4, a combination of the two or vehicle, into one uterine horn of day-5 pseudopregnant rats elicited a huge decidual response. Infusion of indomethacin, an inhibitor of PG synthesis, FPL 55712 (FPL), an antagonist of LTs, or a combination of these inhibitors evoked a minimal decidual response. In addition, FPL infused along with PGE2 or LTC4 markedly reduced the response that could be induced by these arachidonate metabolites alone. Furthermore, infusion of indomethacin along with LTC4 resulted in a far smaller response than that obtained with LTC4 alone. These results are interpreted to indicate that there is an interaction between LTs and PGs in the induction of the uterine decidual response.