Carvedilol, a new beta-blocker with vasodilating properties due to alpha 1-blockade, was investigated in preparations of human ventricular myocardium. Carvedilol demonstrated a high affinity and is a slightly beta 1-selective competitive beta-blocking agent, with a KD for beta 1-receptors of approximately 4-5 nM and a mild selectivity for beta 1 vs. beta 2 receptors of 6- to 39-fold, depending on the method employed to assess subtype potency. In addition, carvedilol was also a potent alpha 1-blocking agent, with a beta 1:alpha 1 blocking relative potency of 1.7-fold. In human lymphocytes containing beta 2-receptors and in human myocardial membranes containing both beta 1- and beta 2-receptors carvedilol exhibited the unique property of guanine nucleotide modulatable binding. Despite this, no intrinsic sympathomimetic activity of carvedilol was detected in preparations of isolated human heart or in myocardial membranes. Vasodilation related to alpha 1-blockade and the lack of intrinsic activity should translate into improved tolerability and good efficacy in the treatment of heart failure.