Plasma levels of both atrial natriuretic factor (ANF) and vasoconstrictor neurohormones are often increased in patients with congestive heart failure (CHF). It has been speculated that ANF is a counterregulatory hormone that influences regional blood flow and sodium balance in human patients by either direct vasorelaxation or by inhibiting the release of other vasoconstrictor neurohormones. The exact relation of increased ANF levels to regional vascular resistance and vasoconstrictor neurohormones has not previously been documented. Thus, we examined the relation between plasma ANF levels, levels of vasoconstrictor neurohormones, and forearm, splanchnic and renal blood flow in 20 normal subjects and in 17 patients with chronic CHF. The plasma ANF level was directly correlated with the plasma norepinephrine concentration (r = 0.83, p < 0.01), plasma epinephrine concentration (r = 0.46, p < 0.01), plasma renin activity (r = 0.50, p < 0.01), plasma angiotensin II concentration (r = 0.79, p < 0.01) and plasma vasopressin concentrations (r = 0.65, p < 0.01). Positive correlations existed between plasma ANF levels and the calculated vascular resistances, i.e., between ANF and forearm vascular resistance (r = 0.41, p < 0.05), splanchnic vascular resistance (r = 0.74, p < 0.01) and renal vascular resistance (r = 0.66, p < 0.05). Serum sodium concentration correlated inversely with ANF (r = -0.66, p < 0.01) as well as with the plasma norepinephrine level (r = -0.54, p < 0.01), plasma renin activity (r = -0.65, p < 0.01), plasma angiotensin II level (r = -0.73, p < 0.01) and plasma vasopressin level (r = -0.42, p < 0.05). Thus, in CHF, despite increased plasma ANF levels, the hypothesized inverse relation of plasma ANF with vasoconstrictor hormones or regional vascular resistances was not observed. Instead, the plasma ANF levels correlated directly with the concentration of vasoconstrictor hormones and regional vascular resistances. These data suggest that ANF is a relatively weak counterregulatory hormone in CHF.