The effect of endothelin (ET)-1 was investigated on resistance arteries of less than 300-microns lumen diameter from the mesenteric circulation, mounted on a wire myograph, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 wk of developing hypertension and in uninephrectomized controls. Arteries from DOCA-salt hypertensive rats presented a significantly reduced external and lumen diameter and increased media width and wall cross-sectional area. Vessels from DOCA-salt hypertensive rats responded to ET-1 with lower active wall tension and media stress. Because the lumen diameter was significantly decreased in DOCA-salt hypertensive rats, the active pressure developed in response to ET-1 was similar in both groups. In contrast, the maximal tension response to arginine vasopressin was enhanced in DOCA-salt hypertensive rats. The sensitivity to both peptides and norepinephrine (NE) was similar in both groups. After removal of endothelium by exposure to the nonionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, ET-1 elicited tension responses that were also lower in DOCA-salt hypertensive rats, whereas NE responses were similar in both groups. These results demonstrate significant morphological and functional changes in small arteries of DOCA-salt hypertensive rats within 2 wk of developing hypertension and blunted reactivity to ET-1. Because similar results were found after removal of endothelium, it is likely that neither prior receptor occupation by endogenous ET nor acute effects of other endothelial cell products play a role in the reduced responsiveness to ET of vascular smooth muscle of small resistance arteries of DOCA-salt hypertensive rats.