The contractile effects of 19 factors on isolated human arterial segments at term pregnancy were quantified, and 14 contractile agents were similarly applied to preterm (23 to 35 weeks) umbilical arteries. Responses to potassium chloride were used to normalize the data. At comparison with the term vessel, the preterm artery contracted more to angiotensin II and arachidonic acid and was more sensitive to oxytocin. Contractions were greater in term arteries to vasopressin, norepinephrine, prostaglandin D2, and prostaglandin E2 but similar in both group of arteries to bradykinin, histamine, acetylcholine, and prostaglandin F2 alpha. Neuropeptide Y, linoleic acid, uridine triphosphate, and thrombin were ineffective. Hyperoxia inconsistently induced weak, short-lived contractions. Contractions to cooling manifested marked desensitization and tachyphylaxis. Serotonin was the only agonist that displayed the pharmacodynamic features most likely to be important for closure: potency, efficacy, and long duration of action (greater than 2.5 hours). It was postulated that cellular elements surrounding umbilical vessels are primary sources of vasoactive agents that are important to closure of the fetoplacental circulation at birth.