Release of atrial natriuretic peptide (ANP) was investigated using the isolated right atrium (RA) cross-circulated with heparinized arterial blood of the donor dog. ANP concentration of the blood was measured by radioimmunoassay. The plasma ANP concentration of the arterial blood of the donor dog (ANP-D) which perfused the RA preparation was 111 +/- 18 pg/ml (n = 4), while the ANP concentration of venous blood leaving the RA preparation (ANP-A) was 1680 +/- 220 pg/ml (n = 4). In comparison, the plasma ANP concentration of venous blood leaving the isolated papillary muscle of the right ventricle (ANP-V) was 106 +/- 19 pg/ml (n = 4), which was not significantly different from the ANP-D concentration. When the right atrium was electrically driven at a rate of 100 beats/min, almost the same rate as the spontaneous sinoatrial rate of 98 +/- 6 beats/min (n = 4), the ANP-A concentration was not changed (1630 +/- 160 pg/ml, n = 4). When the driving rate was increased to 200 beats/min, the ANP-A concentration was significantly increased to 2250 +/- 130 pg/ml (n = 4). These results suggest that ANP is exclusively secreted from the atrium, but not from the ventricle, and that release of ANP is directly related to atrial rate.