Secretion of atrial natriuretic peptide (ANP) depends on the atrial wall distension which may be caused by ventricular pacing. This study was designed to assess the differences in plasma ANP level between DDD and VVI pacing. We measured ANP from venous blood samples using radio-immunoassay in patients with the sick sinus syndrome (n = 8) and atrioventricular block (n = 2) following DDD implantation. Measurement was made under control conditions during DDD and 15-180 min after the pacing mode was changed to VVI and 60 min after returning to DDD. Serum epinephrine (E), norepinephrine (NE), renin (R) and aldosterone (A) levels were also measured prior to and every 30 min after pacing mode changes. The plasma ANP concentration changed from 71.3 pg/ml (normal value) with DDD to 126.8 (15 min), 180.6 (30 min), 221.8 (60 min), 219.2 (90 min), 270.1 (120 min), 145.4 (150 min) and 115.1 pg/ml (180 min) with VVI. It increased markedly, then gradually decreased. It returned to the control value (66.6 pg/ml) in 60 min with DDD, and it reached the peak level with VVI within 60-120 min, and the peak was significantly higher than that for DDD. The increase related to the retrograde ventriculoatrial conduction during VVI pacing. There was no significant change in the NE, E, R and A concentrations. Systolic blood pressure decreased 15 mmHg in VVI and returned to normal by DDD. These results indicated that plasma ANP levels is elevated by VVI pacing, though it was not explained by ventricular pacing alone.