To evaluate the importance of right atrial filling pressure versus central blood volume for the plasma concentration of atrial natriuretic peptide in man, head-up tilt to 50 degrees maintained until the appearance of presyncopal symptoms was carried out in six healthy males. Head-up tilt increased thoracic electrical impedance from 35.4 +/- 0.9 (mean and SE) to 39.2 +/- 0.9 ohm, mean arterial pressure from 64.5 +/- 3.6 to 76.6 +/- 3.0 mmHg and heart rate from 51 +/- 3 to 85 +/- 4 beats min-1 (P less than 0.01). After 35 +/- 7 min presyncopal symptoms appeared, together with a decrease in mean arterial pressure to 51 +/- 4 mmHg and in heart rate to 59 +/- 7 beats min-1 (P less than 0.01). Central venous pressure (2.1 +/- 1.0 mmHg) did not change significantly, but atrial natriuretic peptide decreased from 9.4 +/- 1.6 to 4.2 +/- 1.3 pmol l-1 (P less than 0.01) and was inversely related to thoracic impedance (r = -0.65, n = 44, P less than 0.001). The results indicate that changes in the central blood volume rather than in central venous pressure determine the secretion of atrial natriuretic peptide in man.