The control of uterine blood flow is regulated by a number of factors including vasoactive substances present in the endothelium and the perivascular nerves. We examined the effects of two vasoactive peptides, endothelin and neuropeptide Y, on segments of human uterine arteries and veins in vitro. We found endothelin, a potent vasoconstrictor in the uterine artery and vein, giving a slow and long-lasting contraction starting at 10(-9) mol/L. At this concentration, the established vasoconstrictor noradrenaline had almost no effect. Neuropeptide Y had no effect of its own in the human uterine artery, but increased basal tone in uterine veins, and at higher concentrations triggered spontaneous contractions. Neuropeptide Y (10(-7) mol/L) often, but not always, enhanced the contraction induced by noradrenaline (10(-6) mol/L). Neuropeptide Y (10(-7) mol/L) also enhanced the contraction induced by transmural nerve stimulation (20 Hz, 0.4 msec). We conclude that endothelin and neuropeptide Y may modulate the control of human uterine circulation.