The present study was designed to clarify how atrial appendectomy affects hemodynamics and secretory function of atrial natriuretic polypeptide in the failing heart. Eleven mongrel dogs were prepared for the experimental model of high-output heart failure by creation of arteriovenous fistulas between femoral arteries and veins. Two months after the first operation, effects of bilateral atrial appendectomies on basal and pacing-induced secretions of atrial natriuretic polypeptide were investigated in five dogs with simultaneous measurement of various hemodynamic indices. In the remaining six dogs, used as a control group, pacing-induced secretion of atrial natriuretic polypeptide was examined in the same way as in the appendectomy group. After excision of the atrial appendages, neither systolic blood pressure nor either atrial pressure changed, but plasma atrial natriuretic polypeptide level was decreased (292 +/- 54 to 188 +/- 47 pg/ml, p less than 0.01) and cardiac output fell (3.7 +/- 0.9 to 3.0 +/- 0.8 L/min, p less than 0.01). During pacing-induced tachycardia, the peak level of plasma atrial natriuretic polypeptide was lower in the appendectomy group than in the control groups (593 +/- 213 versus 1170 +/- 324 pg/ml, p less than 0.05), despite similar left atrial pressures in the two groups. The excised appendages contained approximately 30% of the total amount of atrial natriuretic polypeptide. These results demonstrate that atrial appendectomy decreases secretory function of atrial natriuretic polypeptide and reduces cardiac output in dogs with experimental high-output heart failure.