Using vascular smooth muscle cells, the effect of angiotensin II on endothelin receptor regulation was examined. Vascular smooth muscle cells cultivated from human pulmonary artery exhibited high affinity receptors for endothelin-1. When the cells were exposed to angiotensin II, the number of receptors was found to be increased without any change in their affinity. The ligand binding was effectively displaced by BQ123, a selective antagonist for type A endothelin receptor, but not by S6c, a selective ligand for type B receptor, in both control and angiotensin II-treated cells. The level of mRNA coding for the type A receptor was elevated in the latter. These results indicate that angiotensin II up-regulates type A endothelin receptors in human vascular smooth muscle cells through an increase in their corresponding mRNA, suggesting a link between the renin-angiotensin and the endothelin systems.