Clearance and micropuncture studies were performed in 23 dogs without glucose loading to examine the tubule mechanism of renal glycosuria. Studies were carried out in three groups of animals before and after 10% extracellular volume expansion, and administration of maleic acid in low dose at 150 mumol/kg and in high dose at 300 mumol/kg. Specific hexokinase methods were used for the determination of glucose in tubule fluid and urine. Under control conditios, glucose reabsorption occurred predominantly in the proximal tubule. In all three groups, proximal tubule reabsorption of both sodium and glucose was inhibited in the second phase, showing a good correlation between the two. In contrast, fractional urinary glucose excretion remained unchanged after volume expansion and low-dose maleic acid, indicating reabsorption of virtually all the increased glucose load at a further "distal" site. On the other hand, significant glycosuria developed after high-dose maleic acid that was a result of reduced glucose reabsorption in the distal nephron, in addition to the proximal effect. It was concluded that distal glucose transport plays a significant role in regulating urinary glucose excretion and maintains renal thershold for glucose,