Abstract The binding of endothelin (ET) to human placenta ET receptor was strongly inhibited by cadmium ions (Cd 2+) (IC 50 = 2 × 10 −5 M). Experiments with affinity cross-linking showed that the major 40 kDa receptor was inhibited to form a [ 125I]ET-1/receptor complex. The mode of inhibition was noncompetitive with respect to ET-1. The inhibitory effect of Cd 2+ on solubilized ET receptor was partially reversed by the chelating agent, ethylenediaminetetraacetic acid (EDTA), whereas the effect was irreversible for the membrane-associated receptor. The rat aorta contractions by ET were prevented by pretreatment or addition of Cd 2+.