The purpose of the present study was to test the hypothesis that an increased digitalis-like activity, induced by excessive intake of Na, is involved in the development and maintenance of hypertension. In normotensive rats prolonged administration of digitoxin alone induced only a mild and transient rise of blood pressure. Increased intake of NaCl did not affect the blood pressure of these rats. However, simultaneous administration of both digitoxin and NaCl produced a sustained elevation of blood pressure. In SHR the effect of the addition (6% of the weight of the pellets) of 1) NaCl or 2) a mixture containing 50% NaCl and 50% KCl or 3) a mixture containing 65% NaCl, 25% KCl, and 10% MgSO . 7H2O, was examined. A marked fall of blood pressure occurred during the use of the mixtures containing K and Mg. The results suggests that both an increased intake of Na and an increased digitalis-like activity are needed for the development of hypertension. The results on SHR confirm the previous findings demonstrating that the use of salt mixtures in which a part of the NaCl is replaced by K and Mg salts is beneficial compared to the use of NaCl. Furthermore, since K and Mg are effective antagonists of digitalis the results could suggest the involvement of an increased digitalis-like activity in the maintenance of hypertension.