These studies have investigated the effect of endothelin-1 (ET-1) on human resistance vasculature in vivo and in vitro. ET-1 was infused via the brachial artery and forearm blood flow (FBF) measured by venous occlusion plethysmography. Isolated resistance vessels were studied in a myograph. ET-1 (10 pmol-10 nmol/min, i.a.) reduced forearm blood flow. Endothelin-1-induced forearm vasoconstriction was slow to recover following washout. ET-1 (10 pM-10 nM) contracted isolated human subcutaneous and omental resistance vessels. Contractile responses to ET-1 were sustained and washout recovery was slow. Responses to ET-1 displayed marked tachyphylaxis. Calcium channel blockers and removal of extracellular calcium failed to completely abolish responses to ET-1 in vitro.