The present study was done to map the metabolic pathways and rates of maternal plasma clearance of dehydroisoandrosterone sulfate (MCRDS) in pregnancy. In the present study, maternal plasma dehydroisoandrosterone sulfate (DS) metabolism was largely accounted for by two major pathways not present or not prominent in the nonpregnant woman. The first major pathway was clearance of maternal plasma DS by placental aromatization of DS to form estradiol (E2). This pathway accounted for approximately 35 per cent of the total clearance. The second major pathway of metabolism of maternal plasma DS was by 16 alpha-hydroxylation within the maternal compartment. This pathway accounted for approximately 32 per cent of maternal plasma DS clearance. Two other minor pathways of DS metabolism, that is, loss to the fetus and excretion as unaltered DS into urine, accounted for less than 1 per cent of total metabolism in each instance. The final pathway of DS metabolism was excretion as neutral steroids such as urinary 17-ketosteroids and other undefined losses. By combining the rate of DS clearance (MCRDS) from maternal plasma via all pathways with that fraction of DS removed uniquely by placental conversion of DS to estradiol (DS leads to E2), the placental clearance of DS leads to E2 (PCDSE2) may be measured. The measurement of PCDSE2 may be expected to reflect uteroplacental perfusion and as such may provide an investigative tool capable of assessing the dynamics of uteroplacental function in a variety of clinical conditions.