Recently it has been proposed that in renal tubular acidosis the limited renal excretion of hydrogen ion against a concentration gradient might be due to a quantitative defect in energy production from the Kreb''s cycle within the renal tubular cell. Several observations, including our own, have confirmed the finding of low urinary citrate in renal tubular acidosis. Since citrate is an important component of the Kreb''s cycle, it seemed pertinent to measure its excretion in this disease under varying conditions. In an adult with well-documented renal tubular acidosis, studied on a metabolism ward, control values for urinary citrate were 10-15 mgm daily (normal 200-1000 mgm), despite a normal blood pH. Induction of potassium depletion by Diuril and severe acidosis by NH4Cl, caused no change. Repletion with KC1 while acidosis was maintained, produced no rise. After a second period of induced potassium depletion, repletion of this ion, associated this time with a rise of serum pH to normal, again had no influence on citrate excretion. Subsequent administration of NaHCO3 (45 mEq daily) did produce a rise of citrate to low normal levels (maximum 220 mgm daily). When larger amounts of HCO3 (360 mEq daily) were administered, there was a further rise in citrate excretion to more than 500 mgm daily. During four-hour intravenous infusions of either NaHCO3 or tris buffer, citrate excretion reached levels of 300 mgm in four hours, amounts comparable to that seen with induced metabolic alkalosis in normal man. It is postulated on the basis of these observations that defective citrate excretion in renal tubular acidosis is related to an altered tubular intra-cellular environment, possibly acidosis, rather than an enzymatic defect in the Kreb''s cycle. It would thus appear that the low excretion of citrate in this disorder is a secondary rather than primary disorder.