Comparative studies on the actions of serotonin and histamine were carried out on umbilical arteries and veins from humans and sheep and on monkey umbilical veins. All vein preparations and human umbilical arteries were more sensitive to serotonin than to histamine. Tripelen-namine specifically antagonized responses to histamine. Only on monkey umbilical vein strips did histamine produce a greater than serotonin-evoked maximal contraction. These studies suggest that the vasoconstrictor action of histamine has the potential of influencing the umbilical vasculature in vivo.