The resistance of parathyroid cells to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in uremic hyperparathyroidism is thought to be caused, in part, by a 1,25(OH)2D3 receptor (VDR) deficiency in the parathyroids. However, results of biochemical studies addressing VDR numbers in the parathyroids are controversial. Several studies have found VDR content to be decreased in the parathyroids of uremic patients and animals, while others have found no such decrease in the parathyroids of uremic animals. To clarify the role of VDR, we investigated VDR distribution in surgically-excised parathyroids obtained from chronic dialysis patients by immunohistochemistry. We classified the parathyroids as exhibiting nodular or diffuse hyperplasia. Our studies demonstrated a lower density of VDR in the parathyroids showing nodular hyperplasia than in those showing diffuse hyperplasia. Even in the parathyroids showing diffuse hyperplasia, nodule-forming areas were present; these areas were virtually negative for VDR staining. A significant negative correlation was found between VDR density and the weight of the parathyroids. These findings indicate that the conflicting results of biochemical studies may be caused by the heterogeneous distribution of VDR; the decreased VDR density in parathyroids may contribute to the progression of secondary hyperparathyroidism and to the proliferation of parathyroid cells that is seen in uremia.