NKCC1 is a widely expressed isoform of the Na,2Cl,K-cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study we used NKCC1-deficient (NKCC1-/-) and wild type mice (WT) to assess day/night differences of blood pressure (BP), locomotor activity, and renin release, and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24 h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences were not different in NKCC1-/- and WT mice. Spontaneous and wheel running activities in the active night phase were lower in NKCC1-/- than WT mice. In NKCC1-/- mice on a high NaCl diet, MAP increased by 10 mm Hg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 µg/mouse) were significantly greater in NKCC1-/- than WT mice. Plasma renin (ng Ang I/ml hr) and aldosterone concentrations (pg/ml) were higher in NKCC1-/- than WT mice (PRC: 3745 ± 377 vs.1245 ± 364; aldo: 763 ± 136 vs. 327 ± 98). Hyperreninism and hyperaldosteronism were found in NKCC1-/- mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1-/- and WT mice while a low Na diet increased PRC and aldosterone in WT, but not NKCC1-/- mice. We conclude that 24 h MAP and MAP circadian rhythms do not differ between NKCC1-/- and WT mice on a standard diet, probably reflecting a balance between anti- and pro-hypertensive factors, but that blood pressure of NKCC1-/- mice is more sensitive to increases and decreases of Na intake.