1. This study in the canine arteriovenous (AV) fistula model of high-output heart failure (HOHF) evaluated the chronic temporal changes in plasma ANF and pro ANF 31-67 and their relationship to body-fluid balance and the renin-aldosterone axis. In addition, the haemodynamic, hormonal and renal excretory effects of synthetic pro ANF 31-67 infusions were examined in normal and AV fistula dogs with compensated HOHF. 2. Following the construction of the AV fistula, the dogs exhibited chronic parallel elevations in right atrial pressure and the plasma concentrations of ANF and pro ANF 31-67. The gradual increases in the two peptides were associated with a gradual decrease in plasma renin activity and the re-establishment of sodium balance. 3. In normal and compensated AV fistula dogs, synthetic pro ANF 31-67 produced similar significant reductions in arterial blood pressure, right atrial pressure and elevations in urinary sodium excretion. These effects were not associated with increases in plasma or urinary cyclic GMP (cGMP). 4. These results suggest that the elevation in the endogenous circulating levels of pro ANF 31-67 in the AV fistula dogs may represent one chronic adaptive mechanism to achieve body fluid homeostasis. Furthermore, via potentially different mechanisms of action, ANF and pro ANF 31-67 may coordinate and contribute to the regulation of haemodynamic and renal function during physiological and pathophysiological situations.