In contrast to adrenaline, exogenously administered cholinergic agonist, carbachol have very little effect on the contractility of rat cardiac myocytes, unless its contractile has been increased by adrenergic agonist. This interaction between the muscarinic and adrenergic pathways has been suggested to be the major means by which muscarinic agonist alters adrenergic function. When the cardiac myocytes were incubated in the medium contained the mitochondrial respiratory inhibitor potassium cyanide (chemically-induced hypoxia) the spontaneous contractility was ceased. The contractility partly recovered when the cells were exposed to adrenergicstimulation. We showed that during chemical hypoxia, in which cellular ATP is decreased (37% of control), the responsiveness of myocytes to muscarinic cholinergic stimulation significantly increase. Contraction of myocytes, stimulated by adrenaline was totally inhibited by 10(-4)M of carbachol in control cells and 5 x 10(-6)M of carbachol in cells with chemically-induced hypoxia. This increase in physiological response to muscarinic stimulation was associated with an increase of muscarinic receptors (630%). The results support the hypothesis that in ischaemic/hypoxic myocardium the role of cholinergic system may be more important than previously assumed.