Although recent studies have reported endogenous plasma endothelin (ET) levels to be elevated two- to fivefold in chronic pathophysiologic states, whether such an increase in circulating ET levels alone can lead to significant long-term alterations in cardiovascular function is not known. The purpose of this study was to examine the long-term systemic hemodynamic effects of a pathophysiologic increase in circulating ET concentration in chronically instrumented, conscious dogs (n = 4). Infusion of endothelin (2.5 ng/kg/min) for 8 days increased plasma concentration of endothelin two- to threefold. ET increased mean arterial pressure from 85 +/- 3 to 103 +/- 3 mm Hg, which was sustained throughout the period of infusion. Total peripheral resistance was increased by approximately 70%. Cardiac output decreased transiently by 25% and remained below control levels at the termination of ET infusion. These data indicate the importance of pathophysiologic levels of ET in controlling systemic hemodynamics in chronic conditions. Furthermore, ET may play a role as a mediator of chronic hypertension in pathophysiologic states associated with endothelial dysfunction.