Recent evidence from both salt-sensitive humans and several rat models of hypertension indicates an association between metabolic acidosis and genetic hypertension. Preliminary findings of increased renal acid excretion suggest that the perturbation of acid-base status may be the result of increased metabolic acid production. This would be compatible with the previous findings of enhanced Na+/H(+)-antiporter activity, reduced intracellular pH levels, and abnormalities of carbohydrate and lipid metabolism present in both patients with essential hypertension and rat models of genetic hypertension. Further investigation of the factors controlling acid-base metabolism in animal models of hypertension and in salt-sensitive humans may disclose underlying metabolic abnormalities that could account for both the alterations in blood pressure and acid-base status associated with genetic hypertension.