Two experiments were designed to assess the effects of cortisol on prostaglandin-forming cyclooxygenase in 4 gestational tissues of rabbits. Cortisol treatment (12 mg/kg body wt/h) was initiated on day 21 of pregnancy and continued for a 24-h period. In cortisol-treated rabbits, plasma progesterone decreased (P<.01) from 7.2 + or - 0.8 ng/ml on day 21 (pretreatment) to 1.6 + or - 0.2 ng/ml on day 23, 48 hrs after the initiation of cortisol treatment. By 62 h, PGF, PGE2, and cortisol concentrations were all significantly higher (P<.05) in the amniotic fluid of treated animals. However, cortisol treatment did not increase prostaglandin-forming cyclooxygenase activity in fetal or maternal tissues at either 48 or 62 h. Therefore, even though increased prostaglandin production may be responsible for the cortisol-induced abortion, increased cyclooxygenase activity in the gestational compartment was not detected.