The mechanism(s) responsible for the release of brain natriuretic peptide (BNP), a cardiac hormone of ventricular origin, are still not completely understood. We measured plasma atrial natriuretic peptide (ANP) and BNP in 15 subjects (10 men, mean age 67 +/- 3 years) with a dual chamber pacemaker and unimpaired heart function during ventricular pacing, which is known to induce an increase in atrial pressure and plasma ANP concentration. Un der ECG monitoring, all subjects received sequential atrioventricular pacing for 30 minutes and ventricular pacing for 30 minutes, at the same rate of so beats/min. Arterial pressure and plasma BNP and ANP levels were measured every 10 minutes throughout the study. Ventricular pacing led to atrioventricular dissociation in eight subjects and to retrograde ventriculo-atrial conduction in seven. Arterial pressure remained unchanged in all subjects. In the group with atrioventricular dissociation, plasma ANP increased from 10.14 +/- 0.58 to 16.72 +/- 0.92 fmol/mL at the 60th minute (P < 0.0001), whereas plasma BNP did not change at all (from 1.26 +/- 0.07 to 1.16 +/- 0.09 fmol/mL). In the group with retrograde conduction, plasma ANP concentration doubled (from 10.95 +/- 1.66 to 21.40 +/- 1.51 fmol/mL, P < 0.0001), BNP increased 1.5-fold (from 1.16 +/- 0.06 to 1.64 +/- 0.14 fmol/mL, P < 0.001), and the ANP: BNP ratio augmented from 10:1 to 13.4:1. These results indicate that the release of ANP and BNP is regulated by different mechanisms, supporting the view that there is a dual natriuretic peptide system, comprising ANP from the atria and BNP from the ventricles.