The human heart contains both beta 1 and beta 2-adrenoceptors; both mediate positive inotropic and chronotropic effects. In chronic heart failure, beta-adrenoceptor number is reduced, presumably, by down-regulation by endogenous noradrenaline which is elevated due to increased sympathetic activity. Since the human heart contains only a few spare receptors for beta-adrenoceptor-mediated positive inotropic effects and the amount of spare receptors declines in chronic heart failure, it is not surprising that the reduced beta-adrenoceptor number is accompanied by decreased contractile responses to beta-adrenoceptor agonists (including endogenous catecholamines), and the extent of decrease in maximal inotropic response is more pronounced as the disease becomes more advanced. Moreover, in chronic heart failure myocardial G(i)-protein, which inhibits cAMP formation, is increased, which might further contribute to the reduction in beta-adrenoceptor-mediated effects. It appears that, at present, the best therapy for severe heart failure is a successful heart transplant, since in the transplanted heart beta-adrenoceptor number and function seems to be normalized. Moreover, the data currently available do not suggest any development of super- or subsensitivity of postsynaptic cardiac beta-adrenoceptors in the transplanted human heart.