Hemodynamic changes following intravenous administration of SR 42128A (SR), a potent renin inhibitor, were evaluated in normal (N) and sodium-depleted (SD) anesthetized baboons. SR, at 9 mg/kg, decreased arterial pressure (AP) only in the SD group. This effect persisted for at least 2.30 h. At this dose, SR decreased the systemic vascular resistance (SVR) and increased the cardiac output in the SD group more than in the normal group. In both groups, heart rate was slightly increased. However, in the normal group, the highest dose (12 mg/kg) induced the same hemodynamic responses as the dose of 9 mg/kg in the SD group. Every time, plasma renin activity (PRA) was inhibited. Thus, in SD baboons, SR produced a hypotensive effect more pronounced than in the normal group. The dose-related effect on AP seemed to be correlated with the change in SVR. We can conclude that total inhibition of PRA is necessary but not sufficient, under normal conditions, to get an adequate lowering of SVR and a hypotensive effect.