Renal acidification was studied in 10 control subjects and 15 lithium carbonate-treated psychiatric patients of similar age. Seven lithium-treated patients were unable to lower urine pH normally after short duration acid-loading (Li-1:5.35 to 6.25), while 8 (Li-ll:4.52 to 5.17) did not differ from control subjects (4.49 to 5.07). Li-l patients excreted significantly less titratable and net acid than the other groups. Baseline urine pH was higher in both lithium-treated groups than in control subjects, and although this was due in part to the carbonate moiety of the medication, the abnormal minimal urine pH of Li-l patients was not carbonate-dependent. Li-l patients had normal arterial pH and bicarbonate concentrations, trival bicarbonaturia, and no evidence of generalized proximal tubular dysfunction. These data demonstrate that lithium therapy can induce the syndrome of incomplete distal renal tubular acidosis at serum lithium concentrations within the accepted therapeutic range.