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 10 days before telemetric blood pressure and urinary excretion measurements in metabolic cages. On the NS diet, daytime 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 daytime and nighttime MAP of the A₁R+/+ mice increased by ∼10 mmHg, to the same level as that in the A₁R−/−. On the SD diet, day- and nighttime MAP decreased by ∼6 mmHg in both A₁R−/− and A₁R+/+ mice, although the MAP remained higher in A₁R−/− than in A₁R+/+ mice. Although plasma renin levels decreased with increased salt intake in both genotypes, the A₁R−/− mice had an approximately twofold higher plasma renin concentration on all diets compared with A₁R+/+ mice. Sodium excretion was elevated in the A₁R−/− compared with the A₁R+/+ mice on the NS diet. There was no difference in sodium excretion between the two genotypes on the HS diet. Even on the SD diet, A₁R−/− mice had an increased sodium excretion compared with 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.