We studied the effect of an increase in heart rate and/or in right atrial pressure (RAP) on the release of atrial natriuretic peptide (ANP) in 18 patients. In group 1 (n = 6), right ventricular stimulation (100, 120, 140 and 150 bpm) was used to increase RAP by asynchronous contraction of the right atrium and ventricle. Mean RAP increased from 3.9 +/- 0.2 to 8.3 +/- 0.6 mmHg (mean +/- SEM). Median ANP levels increased from 120 to 440 pg ml-1 (P less than 0.05). In group 2 (n = 6), right atrial stimulation below 140 bpm did not have any effect on ANP or RAP, but at a rate above 140 bpm RAP increased from 5.8 +/- 0.5 to 7.5 +/- 0.5 mmHg and ANP from 226 to 396 pg ml-1 (P less than 0.05). In group 3 (n = 6), RAP or ANP were not influenced by continuous right atrial stimulation at 110 bpm. Plasma cyclic GMP levels paralleled the changes in plasma ANP. Thus, an acute increment of RAP results in a release of ANP, but acceleration of heart rate alone has no effect on ANP secretion.