The effect of long-term hydrochlorothiazide therapy on renal calcium excretion was measured in 12 well defined cases of absorptive hypercalciuria and 10 of renal hypercalciuria. Patients were studied during a control phase, at 3 to 6 months of therapy and after long-term treatment with hydrochlorothiazide (mean 61 months for absorptive hypercalciuria and 71 months for renal hypercalciuria). Evaluation comprised measurement of urinary calcium and fractional (intestinal) calcium absorption while patients were maintained on a constant metabolic diet (400 mg. calcium per day) for 3 days. In patients with absorptive hypercalciuria urinary calcium decreased significantly at 3 months of treatment (from 266 to 137 mg. per day, p less than 0.001). However, with continued treatment urinary calcium rebounded to 197 mg. per day. Of the patients with absorptive hypercalciuria 50 per cent were hypercalciuric (greater than 200 mg. per day) on long-term treatment, whereas none was hypercalciuric at 3 months. In contrast, urinary calcium in the patients with renal hypercalciuria decreased from 299 to 104 mg. per day (p less than 0.001) at 3 months of treatment and remained reduced (116 mg. per day) during long-term treatment. Intestinal calcium absorption was increased initially and remained unchanged throughout treatment in the patients with absorptive hypercalciuria. In patients with renal hypercalciuria intestinal calcium absorption decreased significantly after short-term treatment with hydrochlorothiazide and remained so after long-term therapy. The results suggest that, unlike patients with renal hypercalciuria, some with absorptive hypercalciuria lose the hypocalciuric effect of hydrochlorothiazide during long-term treatment.