The kinetics of 11 beta-hydroxysteroid dehydrogenase (11HSD) catalyzing the interconversion of cortisol (F) and cortisone (E) were compared in vitro following incubation of homogenates of human (N = 7) and baboon (N = 2) placenta. In both species, enzyme activity catalyzing the conversion of F to E was associated with the membrane fraction of the cell, was greater in the presence of NAD+ than NADP+, was of similar concentration within the placenta, and exhibited a similar Km for F. Moreover, there was no conversion of E to F in either the baboon or human placenta indicating that in both species, term placenta lacks the 11HSD enzyme catalyzing the reduction of the 11-oxo group of corticosteroids. Significantly, the conversion of F to E by both the baboon and human placenta was inhibited when progesterone was added to the reaction mixture at concentrations equimolar to the substrate. We conclude that 11HSD enzyme kinetics in term baboon placental homogenates are similar to those measured in human term placenta. Moreover, progesterone may be a physiologic regulator of 11HSD in both the human and baboon placenta. Collectively, our findings support the use of the baboon as a model for studies of the regulation of placental corticosteroid metabolism during human pregnancy.