Human placental 11 beta-hydroxysteroid dehydrogenase enzyme has an important role in controlling glucocorticoids reaching the fetus. Excess glucocorticoids impair fetal growth. Recent investigations show that the placenta is rich in NAD- and NADP-dependent 11 beta-hydroxysteroid dehydrogenase activity. Elucidation of the activities of both these isoforms is necessary to understand placental glucocorticoid metabolism. Hence we determined both NAD- and NADP-dependent 11 beta-hydroxysteroid dehydrogenase activities throughout pregnancy. 11 beta-dehydrogenase (oxidative) and 11-oxoreductase (reductive) activities of 11 beta-hydroxysteroid dehydrogenase were determined in 16 first-trimester (9-12 weeks) and 14 second-trimester (13-22 weeks) and 17 term (38-42 weeks) placentae. Both NAD- and NADP-dependent activities increased with pregnancy. The second-trimester NAD-dependent activity was higher than the first-trimester activity (p = 0.02). At term this activity was higher than during the second (p = 0.05) and first (p = 0.0002) trimesters. A similar increase was obtained with NADP isoform except that the difference between first and second trimesters was not significantly different at p = 0.05. The NADH-dependent 11-oxoreductase activity was also detected throughout the pregnancy. However, the activity at term was significantly higher than during the second (p = 0.005) and first (p = 0.001) trimesters. This increase may result in a concomitant increase of cortisol reaching fetus, thus helping fetal lung maturation.