The patch-clamp technique was used to investigate the electrical response of cardiac microvascular endothelial cells to fluid stream applied through a microtube. The fluid stream induced a membrane current whose amplitude was dependent on flow rate. The I-V relationship of the flow-activated current showed a strong inward rectification and a reversal potential close to +30 mV, which gave a P Na /P k =3.47. The inward and outward components of the current nearly disappeared when extracellular Na + and internal K + , respectively, were replaced by NMDG + . Finally, the flow-activated current was fully blocked by 50 μM Gd 3+ and La 3+ . These results show that cardiac microvascular endothelial cells respond to mechanical stimulation associated with flow by increasing their permeability to Na + and K + . This mechanism is suggested to contribute to ionic homeostasis at high heart rates and during post-ischaemic reperfusion.