Oxytocin antagonists may be useful in inhibiting the uterine contractions of preterm labor. One such compound is TT-235 (previously referred to as Antag III). The purpose of this study was to compare the resistance of TT-235 and oxytocin to enzymatic degradation by oxytocinase in the blood of humans and baboons during their 3rd trimester of pregnancy. Blood samples from pregnant women and baboons not in labor were incubated in vitro with known amounts of oxytocin and TT-235. Samples were collected at 0, 15, 30, 45, and 60 min for oxytocin analysis and at 0, 10, 60, and 360 min for TT-235 analysis. Oxytocin was analyzed by radioimmunoassay after extraction, while TT-235 was analyzed by radioreceptor assay. In human blood, oxytocin was readily metabolized with >83% disappearance over the 60-min incubation period. In contrast, TT-235 was stable up to 360 min of incubation. In the baboon, oxytocin did not diminish over the 60-min incubation period. The level of TT-235 was similar to that in human blood without change over 360 min of incubation. This study suggests (1) that in contrast to blood from pregnant humans, blood from pregnant baboons lacks oxytocinase at least in vitro and (2) that TT-235 is resistant to enzymatic degradation by human blood, implying that this oxytocin antagonist may have a prolonged activity in vivo in humans.