Salt and hypertension. Lessons from animal models that relate to human hypertension. A high NaCl diet can raise blood pressure in both susceptible people and in susceptible animals, and the mechanisms are probably quite similar for both humans and animals. The possibly harmful effects of a high NaCl diet are not unexpected since both prehistoric man and mammals evolved in a low NaCl world. Evolutionary forces molded mammals to adapt well to a low sodium intake; the modern high NaCl intake goes "against the grain" of this adaptation. The high NaCl diet can cause premature mortality by raising blood pressure in susceptible people. We have new evidence that in a hypertensive setting, a high NaCl diet can increase mortality even though it does not cause a further rise of blood pressure. Multiple small cerebral infarcts are a partial cause of this excess mortality. Recent evidence also indicates that a high potassium diet reduces the rise of blood pressure caused by a high NaCl diet, whereas a low normal potassium intake encourages an NaCl-induced rise of blood pressure. It is the combination of kidneys that tends to retain NaCl together with a high NaCl intake that produces a rise in blood pressure. This combination tends to cause NaCl retention, which can trigger a rise in blood pressure in susceptible humans and animals. Such a rise in blood pressure can augment renal NaCl excretion and regain the previous NaCl balance. In the Dahl salt-sensitive (DS) rat, there are several renal abnormalities that would tend to encourage sodium retention. By analogy, renal "abnormalities" are probably present in people susceptible to hypertension. 