Beta-blockade has been reported to have beneficial hemodynamic effects in chronic congestive heart failure that may be related to alterations in the abnormal neurohumoral profile characteristic of this population. To determine the relationship of the neurohumoral profile to the hemodynamic response to beta-blockade in patients with chronic congestive heart failure, neurohumoral and hemodynamic variables were measured in 10 subjects having congestive cardiomyopathy at baseline and after administration of the beta-blocker pindolol. Baseline stroke index was noted to have an inverse curvilinear relation with plasma norepinephrine (r = -0.69) and renin (r = -0.71) concentration. Pulmonary vascular resistance demonstrated a direct logarithmic relation with plasma norepinephrine concentration (r = 0.68). Increases in norepinephrine, dopamine, and epinephrine concentrations after dosing were noted, with the most marked increase in norepinephrine concentration being coincident with a significant decline in stroke volume index. Two patients not tolerating beta-blockade were characterized by having baseline norepinephrine concentrations 3 SD higher than those of the remaining patients, more marked increases in epinephrine concentration after dosing, and the most profoundly decompensated heart failure at baseline, as defined by the relationship between neurohumoral and hemodynamic variables. These observations suggest that increases in catecholamines after dosing reflect a compensatory response to the adverse hemodynamic-inotropic effects of beta-blockade in congestive heart failure. The neurohumoral profile and the relationship of neuroendocrine to hemodynamic parameters may be useful in delineating patients at risk for adverse hemodynamic effects of beta-blockade.