If high sodium intake is involved in the pathogenesis of essential hypertension, the effects of changing the sodium intake should be demonstrable in the susceptible part of the normotensive population. Therefore, we have investigated the effects of moderate salt restriction in 52 young normotensive subjects with and without a family history of hypertension; 22 (42%) responded to moderate salt restriction (200 to 50 mmol/day) over 2 weeks, with a significant fall in blood pressure shown by continuous automatic blood pressure recordings. Accordingly, these subjects were classified as salt-sensitive, and the remainder as salt-resistant. Compared to salt-resistant subjects, salt-sensitive subjects showed a 2.5-fold higher incidence of a positive family history of hypertension (p less than 0.01), and a significantly higher blood pressure and lower salivary sodium concentration during the usual high sodium diet. Although there were no differences in Na,K-ATPase activity and in Na-K cotransport of erythrocytes, the pressor response to infused norepinephrine in salt-sensitive subjects was double that of salt-resistant subjects independent of the diet and this was linked to indirect evidence for enhanced proximal tubular sodium reabsorption. On the usual high sodium diet, 40% of the normal population may be salt-sensitive and prone to develop hypertension. Hypersensitivity to catecholamines (genetically determined?) may be the cause of salt sensitivity. A low sodium concentration in saliva deserves further study as a simple screening test to identify salt-sensitive subjects.