In members of hypertensive families a high sodium intake may have a pressor effect. The mechanism mediating the sodium sensitivity is unclear. Blood pressure, exchangeable sodium, plasma levels of norepinephrine, epinephrine, renin and aldosterone, the pressor response to infused norepinephrine or angiotensin II and the urinary excretion of prostaglandin (PG) E2 and F2 alpha were measured after 7 days of low sodium diet (urinary sodium 13 +/- 10 s.d. mmol/24 h) and 7 days of high sodium intake (urinary sodium 268 +/- 97 mmol/24 h) in 10 normotensive men without and 13 men with family history of essential hypertension. After the low sodium phase, blood pressure, heart rate, exchangeable sodium, plasma levels of norepinephrine, epinephrine, renin and aldosterone, pressor doses of norepinephrine or angiotensin II and the urinary excretion of PGE2 or PGF2 alpha did not differ between the two groups. After the high sodium phase, blood pressure increased only in subjects with positive (P less than 0.05) but not in those with negative family history. In the two groups exchangeable sodium increased (P less than 0.05) and plasma levels of NE (-33% versus -32%), renin (-31% versus -27%) or aldosterone (-74% versus -61%) and pressor doses of NE (-55% versus -54%) or ANG II (-72% versus -44%) decreased by a comparable extent. Urinary PGE2 or PGF2 alpha were unchanged. These findings suggest that a high dietary sodium intake exerts a pressor effect in subjects with familial predisposition to essential hypertension. This pressor effect is not explained by an abnormal adaptation of body sodium, sympathetic activity, renin-angiotensin-aldosterone axis, cardiovascular pressor responsiveness and renal prostaglandin excretion to a high sodium diet.