There is ample evidence from animal models indicating that secretion of atrial natriuretic factor (ANF) can be induced by an increase in atrial contraction frequency or atrial distension. The influence of these stimulatory signals on ANF secretion in humans has not been fully elucidated. We assessed the responses to graded right atrial pacing in 28 patients (aged 33 to 70 years) at rates of 100, 125, and 150 beats/min on right atrial pressure, left atrial size (by two-dimensional echocardiography in 9 of 28 patients), and circulating plasma ANF levels. At pacing rates of 125 and 150 beats/min, ANF levels increased from a baseline value of 64 +/- 9 fmol/ml (mean +/- SEM) to 89 +/- 13 fmol/ml (pp less than 0.05) and to 132 +/- 17 fmol/ml, respectively (p less than 0.001). Right atrial pressure increased from a baseline value of 4.1 +/- 0.7 mm Hg to 4.5 +/- 0.6 mm Hg at a pacing rate of 125 beats/min (p less than 0.05) and to 6.1 +/- 0.8 mm Hg at a pacing rate of 150 beats/min (p less than 0.001). Left atrial dimension increased from a baseline value of 44.5 +/- 3 mm to 49.5 +/- 3 mm at a pacing rate of 125 beats/min (p less than 0.05) and increased further to 52.5 +/- 3 mm at a pacing rate of 150 beats/min (p less than 0.001). No significant changes in atrial pressure or size or in plasma ANF were observed at a pacing rate of 100 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)