Prostaglandin F_2α (PGF_2α) is released in increasing quantities from the end of the oestrous cycle in non-primates and the menstrual cycle in primates where it has a role in luteolysis and menstruation, respectively. As prostaglandins are not stored, their release is immediately preceded by their synthesis. The hormones responsible for initiating PGF_2α synthesis in the endometrium are a combination of oestradiol, progesterone and, in some species, oxytocin. The first step in this synthesis involves the release of arachidonic acid, probably by the action of cytosolic phospholipase A₂ (cPLA₂). The first part of this review deals with how these hormones activate cPLA₂, a process that requires intracellular calcium release and phosphorylation of the enzyme. The arachidonic acid released is then converted to PGH₂ by prostaglandin H synthase-2 (PGHS-2 or COX-2). This enzyme is induced in larger amounts in the uterus at the time of increased PGF_2α synthesis. The possible mechanisms involved by which PGHS-2 is induced by the above hormones are discussed in the second part of the review, especially as PGHS-2 apparently does not possess any hormone response elements for steroid hormones. The final part of the review describes the ‘final enzymatic pathway’ by which PGH₂ is converted into PGF_2α. As there is generally a relatively specific increase in PGF_2α synthesis by the endometrium, it would appear that a mechanism exists by which the PGH₂ formed from arachidonic acid by the action of PGHS-2 is directed into the PGF_2α-forming pathway.