The aim of the present study was to elucidate the role of an IV dose of endothelin-3 (ET-3) (5 ng Kg-1 min-1) on mean arterial pressure (MAP), on diuresis and natriuresis in control and in volume expanded anesthetized rats. A systemic infusion of ET-3 in normal rats (Group I) increased MAP and produced a trend of increasing diuresis, without changes in natriuresis. A 10% body weight expansion (Group II) increased diuresis and natriuresis without changes in MAP. The simultaneous infusion of ET-3 and expansion with saline (Group III) resulted in an increase in MAP, an enhanced diuretic response, and a natriuresis of similar magnitude to that observed in Group II. These results suggest that the diuresis produced by a low dose of exogenous ET-3 in control rats, is independent of sodium excretion. Furthermore, the enhanced diuresis caused by ET-3 during expansion is greater than the addition of ET-3 and expansion effects, suggesting that new mechanisms are triggered in order to maintain volume and salt homeostasis in this state.