The Na/Ca exchange is a membrane bound mechanism responsible for net Ca extrusion from the cells. The importance of the Na/Ca exchange is evident from its ability to extrude large Ca loads; however, an additional fundamental aspect of this system results from its capacity, under certain conditions, to work in "reverse" facilitating the net Ca gain and the corresponding increase in the levels of ionized ?Ca! of the cell. The relevance of this function is both physiological and pathological, for the intracellular Ca concentrations regulate cardiac muscle contraction and the contraction of the arterial musculature. Therefore, the understanding of the Na/Ca exchange function can provide insights into the mechanisms leading to the development of hypertension. The present work intends to further characterize the Na/Ca exchanger in relation to the asymmetric properties of the carrier (different reactivity towards intra- and extracellular ligands). The aim is to establish if that asymmetry is intrinsic to the system or a consequence of the different ionic and electrical environments surrounding the intra- and extracellular phases of the cell. This analysis will allow a comparison between data obtained in intact cells and in the membrane vesicles from isolated plasma membranes, widening the field of cellular and molecular research.