Prostaglandins are essential for the initiation of parturition in mice. The peak in uterine prostaglandin F_2α levels occurs at d 19.0 of gestation, just before the onset of labor. Our studies set out to determine the important regulatory step(s) involved in this increase of prostaglandin F_2α. We show that cytosolic phospholipase A₂ mRNA, protein, and activity do not significantly vary during mouse gestation. Rather, our studies demonstrate that cyclooxygenase-1 mRNA is abruptly induced at d 15.5 of gestation, but cyclooxygenase-1 protein levels only gradually increase throughout gestation. In contrast, cyclooxygenase-2 protein remains constant during gestation. We find that prostaglandin F synthase protein increases significantly during gestation reaching peak levels between d 15.5 and d 17.5 of gestation. We also find that the level of prostaglandin dehydrogenase, responsible for degradation of prostaglandins, decreases during late gestation. Taken together these results suggest that the regulation of prostaglandin F_2α is a complex process involving the coordinate induction of synthetic enzymes along with a decrease in degradative enzymes involved in prostaglandin metabolism.