Background/Aims: Increased salt intake and enhanced salt sensitivity are implicated in the pathogenesis of hypertension. The aim of the present study was to investigate whether the urinary excretion rate of Tamm-Horsfall protein (THP) is dependent on salt intake in healthy, genetically hypertension-prone individuals. Methods: Thirty unrelated subjects (13 men and 17 women, mean age 48.1 ± 6.7 years) with at least one first-degree relative with primary hypertension were studied. After a baseline investigation, the study subjects were put on a low-salt diet (10 mmol of sodium and 70 mmol of potassium per day) for 1 week. During the second week, sodium chloride capsules (230 mmol/day) were added to the diet to achieve a high-salt intake of 240 mmol/day. Urine samples (24-hour and overnight collections) were collected before the baseline investigation and at the end of the high- and low-salt diet weeks. The salt sensitivity was calculated as the difference between the blood pressure during high salt intake and the blood pressure during low salt intake. Results: A low salt intake induced a decrease in the urinary excretion rate of THP during the night (11.7 µg/min) compared with baseline (19.5 µg/min; p < 0.05) and high salt intake (23.1 µg/min; p < 0.01). Furthermore, a greater response in blood pressure to a high salt intake, i.e. high salt sensitivity, was associated with increased excretion of THP in urine during the change to high salt intake (r = 0.38, p < 0.05). Conclusion: We were able to confirm that urinary excretion of THP is dependent on sodium intake. Patients with a high salt sensitivity, i.e. an exaggerated blood pressure response to high salt intake, responded to the high salt intake with an even greater increase in the urinary excretion rate of THP. The mechanism underlying this response is still unknown, but it might indicate that distal nephron function in healthy, genetically hypertension-prone individuals is altered.