Studies were performed on anesthetized dogs to determine the relationship of interstitial pressure to sodium excretion during renal vein constriction in the presence and absence of volume expansion. Renal interstitial pressure was measured from implanted capsules during basal renal venous pressure and increased pressures of 10, 20, 30, and 40 mmHg. A positive relationship between renal venous pressure and interstitial pressure was demonstrated in hydropenia and in volume expansion, with markedly higher interstitial pressures obtained in volume expansion. A positive correlation was demonstrated between fractional sodium excretion and renal interstitial pressure in hydropenia as compared to a significant negative correlation in volume expansion. Negative correlations were demonstrated in volume expansion between renal interstitial pressure and glomerular filtration rate and renal blood flow as compared to no significant change in these parameters in hydropenia. Accordingly, a positive correlation was demonstrated between renal interstitial pressure and sodium excretion in hydropenia but not in volume expansion. Volume expansion was characterized by higher interstitial pressure and decreased sodium excretion in association with decreased renal blood flow and glomerular filtration rate.