We studied whether the human heart has spare receptors for β-adrenoceptor-mediated positive inotropic effects. Thus, we assessed in right atria and left papillary muscles of patients with different degrees of heart failure under identical experimental conditions affinity {pK, values from (-)-[125 I] iodocyanopindolol binding} and potency (pD 2 values from contractile responses) for isoprenaline, adrenaline, and noradrenaline in comparison with rat heart. Plots of β-adrenoceptor occupancy versus responses constructed from these data revealed that rat left atria and papillary muscles had a large receptor reserve for all three β-adrenoceptor agonists: 50% of maximal response was produced with only 1–3% of β-adrenoceptor occupancy. In human heart, however, receptor reserve was considerably lower: 50% of maximal response required 8–10%(in right atria) and 20–25%(in left papillary muscles) occupation of β-adrenoceptors. Receptor reserve declined further with an increasing degree of heart failure (and decreasing β-adrenoceptor number): in end-stage heart failure (New York Heart Association class IV) both in right atria and left papillary muscles a 1: 1 ratio between β-adrenoceptor occupancy and responses was observed. These data show that the human heart has only a small receptor reserve for β-adrenoceptor agonists. This may explain why a decrease in β-adrenoceptor number leads to a decrease in β-adrenoceptor function early in the development of heart failure.