The effect of free water diuresis by three different modalities on body 51Cr conservation and distribution was studied in adult male rats. Despite massive diuresis, ADH deficiency had little effect on body 51Cr retention or relative tissue distribution of 51Cr but did induce 25-40% increases in serum 51C concentrations which were reversible by pitressin administration. Glucose feeding produced copious diuresis but no change in body 51Cr retention or relative tissue distribution of 51Cr. The serum 51Cr concentration decreased 23% in association with small increases in serum glucose and insulin concentrations. LiCl administration produced moderate diuresis with little change in body 51Cr retention and inconsistent changes in serum and tissue 51Cr distribution. These data indicate normal body retention of 51Cr despite body water pool turnovers of up to 100% per day. Hence, renal handling of Cr is flow-independent, presumably due to Cr reabsorption at a proximal site within the nephron. However, a marked restriction of Cr filtration by the glomerulus due to protein binding of Cr cannot be ruled out by these data. Differences in body weight, even if assumed to be due to altered extracellular fluid volume, are insufficient to account for the serum 51Cr data. Previous observations in adrenalectomized rats also do not support a role for aldosterone secretion secondary to extracellular fluid volume shifts. Therefore, the increase in serum 51Cr concentration in ADH deficiency may be due to an effect of ADH to promote cellular transport of Cr whereas the decrease in serum 51Cr concentration during glucose feeding is probably due to increased cellular penetration of Cr secondary to insulin action.