The mechanism of the hypotensive response to the intravenous administration of atriopeptin III was investigated in rats of the Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) Okamoto strains. Cardiac performance and the systemic haemodynamic response to acute volume loading were evaluated before and during atriopeptin infusion. Cardiac output was measured by a thermo-dilution technique in conscious rats, and left ventricular pressures with differential (dP/dt) calculations were obtained in anaesthetized animals. Bolus injections followed by a 1-h continuous infusion of atriopeptin caused a progressive decrease in mean arterial pressure (MAP) and cardiac output with no significant change in heart rate. In addition there was a transient decrease, maximal at 5 min, and a subsequent increase in peripheral resistance. Atriopeptin did not alter the maximal cardiac output achieved following acute volume expansion. In the anaesthetized animals, bolus injection with a subsequent 15-min continuous infusion of atriopeptin III significantly reduced left ventricular pressures, dP/dt and mean arterial pressure. Volume expansion fully restored intraventricular pressures and dP/dt while increasing mean arterial pressure toward baseline. We conclude that the steady decrease in mean arterial pressure produced by atriopeptin III is due to a decrease in cardiac output secondary to a fall in stroke volume caused by a lowered filling pressure.