In patients with chronic renal failure due to glomerulonephritis, pyelonephritis or polycystic kidneys the urinary clearance of free chloramphenicol (C(CHL)) was depressed proportionally to GFR (C(In)). The ordinate intercept of the regression line of C(CHL) on C(In), however, consistently was positive (+3 to +5 ml/min). The fractional excretion of chloramphenicol in renal failure increased from its normal value of 50 percent as an exponential function of the decrease of GFR, and as a linear function of the fractional excretion of water or of sodium. Dietary sodium restriction had no influence on C(CHL) in the patients, while water diuresis, in normal subjects, enhanced the urinary excretion of chloramphenicol. The data suggest that chloramphenicol is reabsorbed by back-diffusion and that increases of the rate of flow of urine and tubular fluid prevent back-diffusion.