Coupling of myocardial β-, β1-, β2- and α -adrenoceptors (AR) to myocardial contraction was investigated in patients with various degrees of heart failure. With the use of ΔVcfc, a load independent parameter of myocardial contraction, AR mediated contraction was evaluated. β-AR mediated contraction, ΔVcfc by infusion of a β-AR agonist, isoproterenol, declined with the advancement of heart failure from 0.41 Circ/sec (NYHA I) to 0.31 (NYHA II), 0.22 (NYHA III) and 0.12 (NYHA IV). Dobutamine, a β 1-AR full agonist, mediatedΔVcfc was 92-97% of that of isoproterenol. On the other hand, terbutaline sulfate, a full agonist to β2-AR, increasedΔVcfc partially in comparison with isoproterenol; 51% in NYHA I, 52% in NYHA II, 36% in NYHA III and 17% in NYHA IV. An α 1-AR agonist, methoxamine had little effect on myocardial contractility β -AR and α-AR densities were analyzed by saturation binding isotherms of myocardial membrane fraction with 125I-Iodocyanopindolol (ICYP) and 3H-Bunazosin, respectively. β-1 and β2-ARs were separated by competition binding of 125ICYP with a highly selective β1 AR antagonist, CGP20712A. There was a progressive down regulation of β, β1- and β2-ARs with the advancement of heart failure. A new index was used to examine coupling of ARs to myocardial contracton; Coupling Index. The index was slightly decreased in NYHA II in β - and β1-ARs. In β2-AR, the coupling index declined as heart failure advanced from NYHA I to NYHA IV. These results indicate some mechanism(s) of uncoupling takes place in mild heart failure in β and β1-AR, while in β 2-AR uncoupling progresses from NYHA II to IV. Down regulation of all β -ARs begins from NYHA III on-wards.