Control of hyperparathyroidism is a major goal of the management of bone diseases in chronic dialysis patients. Severity of hyperparathyroidism has been evaluated mainly by the level of parathyroid hormone (PTH), however, parathyroid size can be another critical marker. Patients with larger parathyroid glands are usually more resistant to calcitriol pulse therapy than those with smaller glands. Large parathyroid glands with nodular hyperplasia are composed of cells more resistant to calcitriol due to lower density of calcitriol receptors. Responsiveness to calcitriol therapy was restored by selective destruction of large parathyroid glands (> 0.5 cm3) by ethanol injections under ultrasonographic guidance. Direct injections of calcitriol solution into enlarged glands were also effective in suppressing PTH and restoring responsiveness to calcitriol. These data suggest that size of parathyroid glands reflects the resistance to calcitriol and that prevention of parathyroid hyperplasia is mandatory for the successful medical management of hyperparathyroidism in chronic renal failure.