Oxytocin metabolism seems to occur mainly in the kidney and the liver. Placental cystine amino peptidase (CAP), which inactivates oxytocin by cleavage of the bond between the N-terminal cystine residue and adjacent tyrosine, rises progressively with advancing gestation. The role of CAP in oxytocin metabolism is not clear. To clarify this issue, the authors measure oxytocin metabolic clearance rate(MCR) by the constant infusion of 3mU/min and 6 mU/min synthetic oxytocin in 14 adult subjects: 5 pregnant women (38 approximately 41 weeks gestation), 4 puerperal women and 5 nonpregnant women. Oxytocin MCR (mean +/- SE) during infusion of 3 mU/min was 20.9 +/- 2.6 ml/kg/min in pregnant women; 16.9 +/ 2.4 ml/kg/min in puerperal women; 19.7 +/- 3.3 ml/kg/min in pregnant women. Oxytocin MCR during infusion of 6 mU/min was 22.1 +/- 3.3 ml/kg/min in pregnant women and 22.7 +/- 3.1 ml/kg/min in nonpregnant women. These values were statistically similar. Mean (+/- SE) CAP values were 143.5 +/- 7.8 mU/ml in pregnant women, 60.8 +/- 3.0 mU/ml in puerperal women, and 13.8 +/- 2.7 mU/ml in nonpregnant women. CAP levels in pregnant women were significantly higher than others. 3H-oxytocin degradation was studied in vitro in pooled plasma of pregnant and nonpregnant women. 85% of original 3H-oxytocin was destroyed in pregnant plasma during 1 hour but only below 10% was destroyed in nonpregnant plasma in 2 hours. These results suggest that CAP in pregnant women may not play a role in the inactivation of oxytocin in vivo, thus differing from its role in vitro.