Endothelin is a recently discovered peptide produced by endothelial cells. It has been shown to have potent constrictor effects on major arteries in vitro and to raise rat blood pressure in vivo. The present experiments show that endothelin has a potent constrictor action on the microvasculature. Blood flow changes were measured by a xenon clearance technique in rabbit skin. Endothelin, when injected intradermally into rabbit skin, decreased local blood flow in a dose-dependent manner. Endothelin reduced basal skin blood flow and reversed the increased blood flow induced by a vasodilator. These results show that endothelin, administered extravascularly, has potent vasoconstrictor activity. This adds further support to the suggestion that endothelin may have an important role in the physiological control of blood flow and pressure.