It is well established that increasing degrees of heart failure are accompanied by a reduced density of myocardial β-adrenoceptors. It is unclear, however, whether all β-adrenoceptors in the cardiac cell membrane are coupled to the effector system or whether “spare receptors” or “uncoupled” β-adrenoceptors also exist. To investigate this, we measured the density of β-adrenoceptors and the positive inotropic response to isoprenaline in preparations from the same human hearts. The myocardium from nonfailling hearts had significantly (p<0.01) higher numbers of β-adrenoceptors (104±7 fmol/mg protein) compared with tissue from moderately (mitral valve disease, New York Heart Association [NYHA] class II to II, 60±2.8 fmol/mg protein) and terminally (dilated cardiomyopathy, NYHA class IV, 35±2.7 fmol/mg protein) failing human hearts. The K_D values of the drug-receptor complexes did not differ within the different patient groups. There was a linear relationship (r=0.97) between the β-adrenoceptor density measured and the maximally obtainable positive inotropic effect elicited by isoprenaline in the three groups tested. Thus there seem to be no spare β-adrenoceptors, that is, receptors not required for the production of the maximal inotropic response in the left ventricular human myocardium, and there are no uncoupled β-adrenoceptors. The β-adrenoceptors associated with the plasma membrane (marker: ³H-ouabain binding sites) remained functionally active. In addition, these results indicate that either there is no amplifier system behind the receptor level or it remains unchanged in the failing left ventricular human myocardium under the conditions tested.