We studied the effects of endothelin on the conversion of angiotensin I to angiotensin II in pulmonary artery endothelial cells. Endothelin had a novel effect on angiotensin I conversion. When endothelin was added to pulmonary artery endothelial cells, the conversion of angiotensin I to angiotensin II was enhanced about two-fold. The maximum stimulation was achieved at 10(-8) M of endothelin. This stimulatory effect was suppressed by angiotensin converting enzyme inhibitors such an enalapril. When the calcium antagonist, nifedipine, was incubated with 10(-8) M of endothelin, the conversion of angiotensin I to angiotensin II stimulated with endothelin was slightly suppressed by nifedipine. Enalapril (10(-6) M) completely inhibited the conversion of angiotensin I to angiotensin II in the presence of endothelin. These results suggest that endothelin may play an important role in regulating vascular tone by modulating the conversion of angiotensin I to angiotensin II.