In humans, idiopathic hypercalciuria is associated with stone formation. To study the mechanisms that are responsible for the excess urine calcium excretion in ways that are difficult to impossible in humans, we have developed a rat model of idiopathic hypercalciuria. Hypercalciuric rats were successively inbred for more than 40 generations to produce a strain in which urine calcium excretion is far greater than that of controls and all rats form kidney stones. Analysis of the model has revealed that the rats not only exhibit increased intestinal calcium absorption but an independent defect in renal tubular resorption and an increased tendency for bone demineralization. These findings closely parallel those in patients with idiopathic hypercalciuria. In the intestine, bone, and kidney there is an increased number of vitamin D receptors which appear to make the rats more sensitive to the effect of 1,25(OH)2D3. Whether the increased number of vitamin D receptors can be directly translated into hypercalciuria and whether the same abnormality is present in humans with idiopathic hypercalciuria remains to be determined.