In the baboon fetus, the conversion of cortisol (F) to cortisone (E) [80%] exceeds the reverse reaction [15%]. Since the fetus is exposed to high quantities of E throughout most of pregnancy, we determined whether F to E interconversion is altered following acute changes in serum E. Adult female baboons (N = 3) were sedated with ketamine, constantly infused for 180 min via an antecubital vein with 15 microCi[14C]E and 15 microCi[3H]F, and saphenous vein blood samples obtained at 70, 80 and 90 min. At 90 min, an infusion of E (166 micrograms/min) was initiated and blood samples obtained at 160-180 min. This protocol was repeated in the same animals treated 24 and 3 h prior to infusion with 3 mg betamethasone. Metabolic clearance (MCR), transfer constants (%) and serum levels (microgram/dl) of F and E were determined. E increased (P less than 0.05; paired t) MCR-E, and serum F and E levels in control and betamethasone-treated baboons. E also decreased %F to E in betamethasone-treated but not control animals. These findings suggest that acute changes in serum E alter MCR-E, do not influence the conversion of E to F and may decrease the conversion of F to E. Therefore, we suggest that the high conversion of F to E in the baboon fetus is probably not the result of elevated concentrations of E.