We have studied the effect of non-depolarizing neuromuscular blocking agents, at concentrations present in serum during anaesthesia, on release of [3H]-norepinephrine ([3H]NE) from superfused atrial appendage obtained during cardiac surgery from 48 patients. Three of the neuromuscular blocking agents (pancuronium, gallamine and rocuronium), which are known to cause an increase in heart rate during anaesthesia, increased stimulation-evoked release of [3H]NE. In contrast, (+)tubocurarine and pipecuronium, neuromuscular blocking agents that do not cause tachycardia, did not affect release of NE. Org 9487 significantly enhanced release while SZ1677 was ineffective, even at concentrations higher than those expected after administration of a 2 x ED95 dose. Atropine enhanced release. These data suggest that the axon terminals of sympathetic nerves in human heart have muscarinic heteroreceptors whose activation by acetylcholine (ACh) released from the vagal nerve reduces release of NE. This action contributes to lowering of heart rate. Therefore, any neuromuscular blocking agent with antimuscarinic actions and capable of increasing the release of NE may produce tachycardia.