A previous study reported that urinary markers of protein intake are inversely related to blood pressure via unknown mechanisms. In man and rats, protein intake affects renal function and increases renal sodium excretion. The present study investigates the relation between markers of protein intake and blood pressure and the possible role of sodium in this relation. Blood pressure status, overnight urinary urea as index of protein intake, urinary and plasma sodium, and other variables were measured in a population sample of 3705 men and women, aged 25-74 years, without high plasma creatinine. Urinary urea was inversely related to blood pressure and hypertension: in multivariate analyses, 6.5 mmol/h higher urinary urea (about one s.d. in men and women) was related to 4.25 mm Hg lower systolic blood pressure (95% confidence interval = 1.34-8.49), and to 0.65 lower risk of hypertension (95% CI 0.34-0.87). An interaction was found between overnight urinary sodium and the relation of urinary urea to blood pressure: the relation was significant only in persons with overnight urinary sodium above the median. Urinary urea was significantly and inversely also related to plasma sodium. Data confirm an inverse relation to blood pressure of protein intake as measured by urinary urea. The possibility of sodium-related mechanisms is supported by the interaction of urinary sodium with the relation and by the inverse association of urinary urea with plasma sodium. The hypothesis is made that high protein intake could counteract sodium-dependent blood pressure rise via stimulation of renal sodium excretion.