The effects of adding exogenous reduced glutathione (GSH) to the perfusate were studied in the isolated perfused rabbit kidney. The addition of 500 mg/liter of GSH to the perfusate prevented the depletion of cortical and medullary GSH; perfusion without the addition of GSH consistently resulted in depletion of tissue levels of this tripeptide. In addition, GSH supplementation of the perfusate decreased renal vascular resistance and increased perfusate flow. GSH extraction studies revealed a progressive decrease in renal extraction with time, ranging from complete extraction at 10 min to a value of 38% at 60 min. The fractional clearance of GSH increased from 7.3% at 10 min to 17.9% after 60 min of perfusion. The results indicate a high affinity of the rabbit kidney for GSH and a relatively large net reabsorption of the tripeptide. © 1976.