We investigated whether a postsynaptic sensitization by halothane for beta-adrenoceptor-mediated effects occurs in diseased human myocardium. In addition, we hoped to achieve further insights into the cellular mechanism and, in particular, the role of M-cholinoceptors and beta-adrenoceptors. The experiments were performed on isolated, electrically driven atrial and ventricular preparations and membranes isolated from human hearts obtained at cardiac surgery. Halothane concentration-dependently reduced binding of [3H]quinuclidinylbenzilate ([3H]QNB) to M-cholinoceptors but had no effect on equilibrium saturation binding of 125-iodocyanopindolol (125I]Cyp) to beta-adrenoceptors. High-and low-affinity states of agonist binding of carbachol to M-cholinoceptors were not affected, but halothane inhibited high-affinity binding of isoprenaline to beta-adrenoceptors. In contrast, halothane augmented the potency and efficacy of the positive inotropic effect of isoprenaline in atrial and ventricular myocardium. The "direct" negative inotropic effect in atrial and the "indirect" negative inotropic effect in ventricular myocardium by M-cholinoceptor stimulation with carbachol was unchanged by halothane. We conclude that in human atrial and ventricular myocardium a sensitization to catecholamines is induced by halothane, the mechanism of which is likely to be located at the postsynaptic level of the sympathetic neuroeffector junction. Facilitated coupling of beta-adrenoceptors or an uncoupling of M-cholinoceptors with reduced negative inotropic effects of agonist does not play a role. We showed that sensitization of this system apparently is due to direct actions of halothane on the G-protein-coupled adenylate cyclase complex.