Addition of endothelin-1 (ET-1) to primary cultures of bovine adrenal chromaffin cells causes a significant enhancement of norepinephrine and epinephrine efflux, with an EC50 of about 1 nM. A maximally effective concentration of endothelin (10 nM) gives a transient increase in noradrenaline release within 5 min. The amounts of noradrenaline and adrenaline released by ET-1 was smaller than the release elicited by maximally effective concentrations of bradykinin or prostaglandin E2. These results raise the possibility that the vascular endothelium may stimulate release from chromaffin cells by production of ET-1.