We investigated the influence of shear-stress on Xenopus and rat epithelial sodium channels (xENaC and rENaC, respectively) expressed in Xenopus oocytes. Whole-Cell currents were measured using the two-electrode voltage-clamp technique. Shear-stress was generated by a gravity-driven fluid-stream using a Pasteur pipet which was placed about one oocyte-diameter above the oocyte and perfused with a flow-rate of 3 ml/min. This fluid-stream induced shear-stress stimulated the amiloride-sensitive current (I_Na) by 32 ± 4 % in xENaC and 24 ± 5 % in rENaC-expressing oocytes. The stimulation did not occur in control-oocytes and was completely blocked by 10 mM amiloride. To proof the idea of stimulation due to ENaC-activation, we tried to activate ENaC prior to shear-stress, which should inhibit the effect. Activation of ENaC by 100 mM glibenclamide completely inhibited shear-stress induced currents (I_ss). Stimulation by 20 mg/ml trypsin increased I _ss, but interestingly the ratio of I_ss was constant prior to and after trypsin. It is suggested that trypsin could activate silent channels present on the oocyte surface, which escaped protease-cleavage in golgi-apparatus, that is likely to be the reason for the increased I_ss following trypsin application. Taken together, these data indicate that ENaC responds to mechanical stimuli, representing a new regulatory mechanism for the physiology of epithelial function. Supported by DFG, FR2124