Elevated plasma noradrenaline concentrations in patients with low-output cardiac failure: dependence on increased noradrenaline secretion rates. 1. Plasma noradrenaline concentrations are elevated in patients with congestive heart failure; however, the pathogenesis of these elevated noradrenaline levels is controversial. 2. Possible mechanisms for elevated noradrenaline concentrations in patients with congestive heart failure include increased noradrenaline secretion, decreased clearance of noradrenaline, and a combination of increased secretion and decreased clearance. 3. In the present study, plasma noradrenaline clearance and apparent secretion rates were determined using a whole-body steady-state radionuclide tracer method in six otherwise healthy patients with moderate degrees of low-output cardiac failure and in six normal control subjects. 4. The venous plasma noradrenaline level was elevated in the patients with congestive heart failure as compared with the control subjects (4.18 +/- 1.34 versus 1.54 +/- 0.16 nmol/l, P less than 0.05). There was no stimulation of the adrenal medulla as evident by normal plasma adrenaline levels in both groups (0.19 +/- 0.04 versus 0.18 +/- 0.02 nmol/l, not significant). The apparent secretion rate of noradrenaline was elevated in the patients with congestive heart failure (4.75 +/- 1.95 versus 1.78 +/- 0.18 nmol min-1 m-2, P less than 0.05), whereas the clearance rate of noradrenaline was similar in the two groups (1.26 +/- 0.27 versus 1.16 +/- 0.02 l min-1 m-2, not significant). 5. We conclude that the high peripheral venous plasma noradrenaline concentrations in patients with mildly decompensated low-output cardiac failure are initially due to increased secretion, rather than to decreased metabolic clearance, perhaps in response to diminished effective arterial blood volume. 