The effect of 25 mg. hydrochlorothiazide twice daily on the meta-phylaxis of recurrent calcium lithiasis was compared to placebo in a double-blind study during 1 year in 51 patients. A distinct and continuous decrease in urinary calcium excretion occurred only in patients given hyrochlorothiazide. On the other hand, both groups showed a slight increase in total serum calcium levels, unchanged values for ionized and ultrafilterable calcium, and decreased urinary excretion of oxalate during the study. The activity products of calcium oxalate and calcium phosphate also were decreased in both groups but remained within the metastable range. Spontaneous passage of renal stones occurred during treatment in 6 patients given placebo and in 6 treated with hydrochlorothiazide despite decreased urinary calcium excretion in the latter group. The findings show the specific effect of hydrochlorothiazide treatment to be a decrease in urinary calcium excretion in patients with calcium lithiasis, while other changes appear to be nonspecific effects of treatment.