We examined the salt-losing tendency of chronic renal failure in five patients with glomerular filtration rates varying from 5.2 to 16.0 ml per minute. When the studies began, patients were in sodium balance on metabolic diets containing 58 to 342 meq of sodium daily. The sodium content of the diet was then reduced in stages at intervals of at least one week over four to 14 weeks with careful clinical and laboratory monitoring. In four of the patients a salt-losing tendency developed, temporarily requiring intravenous salt replacement in two. At the completion of the studies all the patients remained in sodium balance while ingesting a mean (+/- S.D.) of 5.0 +/- 2.9 meq of sodium per day. There was no change in renal function. Thus, the salt-losing tendency of chronic renal failure is reversible and appears to be a manifestation of the long-term adaptation for sodium excretion.