Reserpine induced supersensitivity to norepinephrine (NE) in rat vas deferens was sought by alteration of Mg++ and Ca++ concentration in incubation medium in the absence and presence of EDTA. Vas deferens incubated in Mg++ free and Mg++ excess media showed supersensitivity and subsensivity to NE respectively. Alterations in the sensitivity to NE produced by varying the concentrations of Mg++ were comparatively less. In the presence of EDTA, vas deferens obtained from reserpinized animals showed subsensitivity in normal and Mg++ excess media and supersensitivity in Mg++ free medium. In the presence of EDTA, reserpinized preparations showed slight supersensitivity in normal Mg++ medium, marked supersensitivity in Mg++ free and lesser subsensitivity in Mg++ excess medium. Probably EDTA by more effectively removing Mg++ from the membrane binding sites by chelation makes the membrane permeable to Ca++ leading to supersensitivity to NE (observed only in the presence of EDTA). These results suggest that the failure of reserpine to induce supersensitivity to NE in rat vas deferens may be due to an enhanced antagonism of Mg++ on Ca++ movements in this preparations due to the poor capacity of rat tissue to retain Ca++.