In patients with congestive heart failure, atrial natriuretic factor may serve as a counter-regulatory hormone, offsetting the vasoconstrictive and volume-retentive effects of the sympathetic nervous system, the renin-angiotensin-aldosterone system and vasopressin. Indeed, the plasma levels of atrial natriuretic factor and the vasoconstrictor hormones are often simultaneously elevated in these patients. It is not known, however, whether atrial natriuretic factor remains responsive to sudden reductions in atrial pressure in patients with chronic heart failure, or is unresponsive like the vasoconstrictor systems. To examine this issue, the plasma concentrations of atrial natriuretic factor and the vasoconstrictor hormones were measured in 20 normal subjects and 12 patients with chronic congestive heart failure during incremental lower body negative pressure, an intervention that lowers atrial pressure. In the normal subjects, incremental lower body negative pressure at -10, -20 and -40 mm Hg decreased central venous pressure and pulse pressure. At maximal lower body negative pressure, plasma atrial natriuretic factor levels decreased from 51 ± 5 to 27 ± 3 pg/ml (p < 0.01), whereas increases occurred in plasma levels of norepinephrine (194 ± 11 to 385 ± 70 pg/ml, p < 0.01), renin activity (1.4 ± 0.2 to 3.9 ± 0.1 ng/ml per h, p < 0.01) and vasopressin (1.3 ± 0.1 to 6.4 ± 2.4 pg/ml, p < 0.05). In the patients with congestive heart failure, lower body negative pressure also reduced central venous pressure. Baseline plasma atrial natriuretic factor levels were markedly elevated, averaging 438 ± 138 pg/ml, and decreased to 317 ± 87 pg/ml at maximal lower body negative pressure (p < 0.05). In these patients, lower body negative pressure did not change plasma norepinephrine (614 ± 113 to 754 ± 128 pg/ml), renin activity (5.6 ± 1.1 to 5.8 ± 0.9 ng/ml per h) or vasopressin (4.2 ± 1.0 to 7.2 ± 1.9 pg/ml) (all p = NS). Unlike vasoconstrictor hormone secretion, atrial natriuretic factor secretion remains responsive to reductions in atrial pressure. A dynamic role for atrial natriuretic factor would underscore its potential to regulate vascular resistance and sodium excretion during changes in posture or volume status in patients with congestive heart failure.