Chlorthalidone promotes mineral retention in patients with idiopathic hypercalciuria. In seven patients with severe idiopathic hypercalciuria and recurrent calcium oxalate nephrolithiasis, we have determined the effects on mineral balance of chronic treatment with chlorthalidone or trichlormethiazide, drugs that are widely used to lower urine calcium losses and reduce stone recurrence. Each person excreted above 350 mg of calcium daily while untreated, and was studied twice, before and after three to six months of treatment. Compared to pretreatment, the drugs reduced intestinal calcium absorption; but they reduced urine calcium loss even more, so calcium retention increased. Phosphate retention also increased. Serum levels of calcitriol, parathyroid hormone, calcium, phosphate, and magnesium were unchanged. At least in patients of this type, chlorthalidone and trichlormethiazide seem ideal treatments, that lower urine calcium yet increase calcium and phosphate retention. Whether patients with less severe hypercalciuria respond this way is unknown.