• Urinary excretion of N-acetyl-β-glucosaminidase (NAG), a lysosomal enzyme, was examined In 33 children with hypercalciuria. Urinary NAG excretion In 13 healthy children was 5.84±9.35 nmole/hr/mg of creatinine (NAG/Cr) (mean±SD) compared with 35.61±42.04 nmole/hr/mg of creatinine in 23 children with renal hypercalciuria, and 28.99 ±13.69 nmole/hr/mg of creatinine In ten children with absorptive hypercalciuria. In children with renal hypercalciuria, NAG/Cr excretion was not statistically different between children with either urolithiasis or hematuria without calculi. In six children with renal hypercalciuria, no significant change in NAG/Cr excretion occurred after a mean duration of 25 weeks of hydrochlorothiazide therapy although urinary calcium to creatinine ratios (UCa/Cr) decreased from 0.24±0.11 to 0.16±0.11. We conclude that increased urinary calcium excretion produces renal tubular injury and that the renal injury may not be reversed by short-term alterations in urinary calcium excretion.