Urinary excretion of sodium and water was investigated in patients with chronic end-stage renal disease before and after three different experimental manipulations: reduction in urea solute load by dialysis while extracellular fluid volume (ECFV) was maintained, dialysis without alteration in urea solute load or ECFV and reduction in ECFV without alteration in urea solute load. Sodium and water excretion significantly declined in association with a reduction in both urea solute load and ECFV, but not during a dialysis when reduction on both of these indexes was prevented. The excretory changes occurred in the absence of any alteration in creatinine clearance. The studies suggest that both solute load and the degree of extracellular fluid volume expansion contribute independently to the rate of sodium and water excretion in chronic renal disease. It is concluded that in any given patient the overall excretion of sodium and water is directly influenced by a number of factors including the solute load, the degree of ECFV and the glomerular filtration rate.