The effect of endothelin-1 (ET-1) and endothelin-3 (ET-3) on the proliferation of aortic vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) was assessed by the measurement of (3H)-thymidine incorporation into DNA. ET-1 and ET-3 stimulated the DNA synthesis in a dose-dependent manner. ET-3 was less potent than ET-1 in its stimulatory activity. The increase in (3H)-thymidine incorporation is clearly attenuated by Atriopeptin III (ANP 5-28). Atriopeptin I (ANP 5-25), a ANP fragment with the reduced biological activity compared to ANP 5-28, has no effect on the endothelin mediated stimulation of DNA-synthesis.