It is now established that cells in many tissues including renal epithelial cells and perivascular sensory nerves have mechanisms that monitor and respond to the concentration of Ca2+ in the interstitial compartment [Ca2+(ISF)]. We tested the hypothesis that high Na+ intake alters renal [Ca2+(ISF)] and that the response is altered in salt-sensitive hypertensive versus normotensive rats. Male Wistar (W), Dahl salt-resistant (DR), and Dahl salt-sensitive (DS) rats were fed diets containing 0.45% or 8% NaCl for 7 days beginning at 8 to 10 weeks of age. Systolic blood pressure (BP) was measured before and at the end of the 7-day period. During the last 12 h the animals were placed in metabolic cages for urine collection. They were then anesthetized and renal [Ca2+(ISF)] was determined using in situ microdialysis. Feeding 8% NaCl caused a significant increase in systolic BP only in DS. The 8% NaCl also caused a significant increase in renal urinary Na+ excretion in all groups, had no effect on renal Ca2+ excretion in W or DS and significantly increased urinary Ca2+ excretion in DR. When fed 0.45% NaCl, renal [Ca2+(ISF)] was lower in W and DR compared with DS. Feeding 8% NaCl significantly increased [Ca(ISF)] in W, had no effect on this parameter in DR, and significantly decreased [Ca2+(ISF)] in DS ([Ca2+(ISF)] for DS on 0.45% NaCl = 1.89 +/- 0.15 v 8% NaCl = 1.08 +/- 0.07 mmol/L, n = 6 to 12, P <.05). These results indicate that Na+ loading significantly alters renal [Ca2+(ISF)]; that the response of DS is disturbed relative to controls, and are consistent with the hypothesis that Na+ loading can alter cell function by modulating [Ca2+(ISF)].