Prostaglandins play an important role in reproduction, particularly in pregnancy and parturition. We investigated the expression of prostaglandin endoperoxide H synthase (PGHS) 1 and 2, key enzymes in prostaglandin biosynthesis, in the human placenta at term. Northern blot analysis of placenta total and poly(A)+ RNA failed to detect significant levels of PGHS-1 mRNA, using a human PGHS-1 specific DNA probe. In contrast, definite PGHS-2 mRNA bands, with a calculated size of about 4.5 kb, were observed in Northern blots of placenta poly(A)+ RNA, using a PGHS-2 specific DNA probe. Moreover, PGHS-1 and PGHS-2 expression was assessed at the translational level by Western blot analysis. Thus, using three highly specific antibodies, we found a selective expression of PGHS-2 immunoreactive protein. These results indicate that PGHS-2 is the PGHS isoform prevalently expressed in the human placenta at term and support the hypothesis that PGHS-2 plays a prominent role in the maintenance of pregnancy, in line with the proposed anti-apoptotic and growth promoting properties of this enzyme.