We have shown previously that an extract of atrial tissue from rat heart contains a potent natriuretic factor. In this study anesthetized rats were connected to a respirator and the right atrial appendage was either excised, using a loop ligature (experimental group), or the loop was placed around the appendage and then removed (sham-operated group). After equilibration and control urine collection periods an isooncotic Ringers-albumin solution was infused intravenously (25% of estimated blood volume), and renal function was monitored over the next hour. There were no differences between groups in control period arterial or central venous pressures, heart rates, cardiac outputs, renal blood flows, or filtration rates. However, the diuretic and natriuretic responses to infusion in the experimental group were only one half of those in the sham-operated series (vol = 23.4 +/- 6.2 vs. 68.2 +/- 11.0 microliter X min-1 X g kidney wt-1, UNa V = 2,731 +/- 856 vs. 6,504 +/- 962 nmol X min-1 X g kidney wt-1). These differences were not affected by prior bilateral vagotomy. Administration of homologous atrial natriuretic factor or furosemide resulted in identical renal responses in both groups. We conclude therefore that acute hypervolemia is associated with release of atrial natriuretic factor into the bloodstream and that removal of the atrial appendage reduces the amount available for such release.