The aim of this study was to investigate: 1) the effects of treadmill exercise on plasma catecholamines and endothelin-1 (ET-1, a potent vasoconstrictor) levels in hypertensive patients; and 2) the impact of 1-month therapy with losartan as compared with moxonidine on catecholamine and ET-1 changes during exercise. Twenty-eight patients with essential hypertension were randomized in two groups: group A received losartan and group B received moxonidine for 1 month. Plasma catecholamines exhibited an almost 10-fold increase during exercise (p<0.00001) before treatment. Moxonidine significantly decreased catecholamine levels (p<0.05), while losartan reduction was nonsignificant (p<0.36). Plasma ET-1 increased significantly during exercise before treatment (p<0.00005). Moxonidine therapy did not affect ET-1 levels (p<0.88), while losartan resulted in a significant decrease of ET-1 levels both at baseline and during exercise (p<0.007). These findings suggest a mechanism for the reduced cardiovascular mortality noted with an angiotensin receptor blocker as compared with a sympatholytic agent.