The rest and exercise hemodynamic-inotropic response to administration of the beta-blocker pindolol was evaluated in 10 patients with congestive cardiomyopathy to determine whether the intrinsic sympathomimetic activity (ISA) of this agent may preserve ventricular function in the setting of beta-blockade. A significant (p less than .05) rise in systemic and pulmonary vascular resistance and a decline in stroke volume and cardiac index was observed after a single 10 mg dose. The change in cardiac index was negatively correlated with free drug concentration (r = -.59, p less than .01); the change in pulmonary and systemic vascular resistance showed a positive correlation with plasma concentration (r = .67, r = .57, respectively; all p less than .05). The response to exercise reflected a predominant beta-blocking effect, with a significant decrease in peak heart rate and cardiac index and an increase in pulmonary vascular resistance. There were no significant changes in variables of right or left ventricular inotropy after administration of the drug. The mean baseline plasma norepinephrine concentration for the population was 609 +/- 172 pg/ml (normal = 196 +/- 7 pg/ml) and was markedly elevated in two patients (931 and 2053 pg/ml) who developed severe pindolol-induced hypotension. Renin increased markedly in these two patients, but decreased in each of the remaining eight patients. These data indicate that although inotropy is not adversely affected by pindolol, increased afterload, which appears to be mediated by peripheral beta-blockade, results in a reduction in ventricular performance.(ABSTRACT TRUNCATED AT 250 WORDS)