The present study was performed to investigate the role of adenosine A₁ receptors in regulating blood pressure in conscious mice. Adenosine A₁ receptor knockout (A₁R-/-) mice and their wild-type (A₁R+/+) littermates were placed on standardized normal-salt (NS), high-salt (HS) or salt-deficient (SD) diets for a minimum of ten days prior to telemetric blood pressure and urinary excretion measurements in metabolic cages. On a NS-diet day- and nighttime mean arterial blood pressure (MAP) was 7-10 mmHg higher in A₁R-/- than in A₁R+/+ mice. HS-diet did not affect the MAP in A₁R-/- mice, but the day- and nighttime MAP of the A₁R+/+ mice increased by ~10 mmHg to the same level as that in the A₁R-/-. On a SD-diet, day- and nighttime MAP decreased by ~6 mmHg in both A₁R-/- and A₁R+/+ mice, although the MAP remained higher in A₁R-/- than A₁R+/+ mice. Although plasma-renin levels decreased with increased salt intake in both genotypes, the A₁R-/-mice had a ~2 fold higher plasma-renin concentration on all diets compared to A₁R+/+ mice. Sodium excretion was elevated in the A₁R-/- compared to the A₁R+/+ mice on NS-diet. There was no difference in sodium excretion between the two genotypes on HS-diet. Even on a SD-diet, A₁R-/- mice had an increased sodium excretion compared to A₁R+/+ mice. An abolished tubuloglomerular feedback response and reduced tubular reabsorption can account for the elevated salt excretion found in A₁R-/- animals. The elevated plasma-renin concentrations found in the A₁R-/- mice could also result in increased blood pressure. Our results confirm that adenosine, acting through the adenosine A₁ receptor, plays an important role in regulating blood pressure, renin release and sodium excretion.