A high sodium (HS) intake is associated to increased cardiovascular and renal risk, especially in overweight subjects. We hypothesized that abnormal sodium and fluid handling is involved, independent of hypertension or insulin resistance. Therefore, we studied the relation between BMI and sodium-induced changes in extracellular fluid volume (ECFV; distribution volume of 125I-iothalamate) in 78 healthy men, not selected for BMI. A total of 78 subjects with a median BMI of 22.5 (range: 19.2–33.9 kg/m2) were studied after 1 week on a low sodium (LS) diet (50 mmol Na /d) and after 1 week on HS (200 mmol Na /d). The change from LS to HS resulted in an increase in ECFV of 1.2 ± 1.8 l. Individual changes in ECFV were correlated to BMI (r = 0.361, P Na = [Na ] × GFR, r = 0.281, P Na during HS. Although no hypertension occurred in these healthy subjects, our data provide a potential explanation for the interaction of sodium intake and BMI on cardiovascular and renal risk. Exaggerated fluid retention may be an early pathogenic factor in the cardiorenal complications of overweight.