Serum concentrations of dehydroepiandrosterone (D) are greater and those of D sulfate (DS) are lower in female baboons than in women, suggesting interspecies differences in relative production and catabolism of these steroids. To examine this possibility, the metabolic clearance rate (MCR), interconversion (rho), and production of D and DS were determined in five adult female baboons by constant intravenous infusion of [3H]DS and [14C]D. MCR-D (mean +/- SE) was greater (407 +/- 72.8 1/day; 23.1 +/- 3.4 1/day.kg, P less than 0.01) than MCR-DS (44 +/- 5.7 1/day; 2.5 +/- 0.3 1/day.kg). rho-D leads to DS (mean % +/- SE) was greater (45.4 +/- 3.0, P less than 0.001) than rhoDS leads to D (3.8 +/- 0.6), indicating that the equilibrium favors DS formation. Calculated D production and secretion rates were similar (4.5 and 4.4 microgram/min, respectively), whereas DS production (4.1 microgram/min) was twice its secretion rate (2.1 microgram/min). The large difference between MCR-D and MCR-DS resembles that in human beings. However, when clearance is expressed per kilogram body weight, MCR-D is similar to that in man, but MCR-DS is approximately 15-fold greater in the baboon. It is concluded that compared to values in human beings, the greater MCR-DS in baboons maintains the lower serum DS concentration, whereas the higher serum D levels probably result from the relatively greater secretion rate of D baboons.