The factors involved in abnormal parathyroid cell secretory function and growth in patients with primary (I degree) and secondary (II degree) hyperparathyroidism are still incompletely understood. We compared the expression of the calcium-sensing receptor (CaR) at the gene message and the protein level in parathyroid tissue obtained from patients with I degree non-uremic or II degree uremic hyperparathyroidism with that in normal parathyroid tissue, using in situ hybridization and immunohistochemistry techniques. The expression of the CaR mRNA and protein was reduced in most cases of I degree adenoma and II degree hyperplasia, compared with strong expression normal parathyroid tissue. In II degree hyperparathyroidism, expression of both receptor mRNA message and protein was often particularly depressed in nodular areas, compared with adjacent non-nodular hyperplasia. Decreased Ca-R expression in adenomatous and hyperplastic parathyroid glands would be compatible with a less efficient control of PTH synthesis and secretion by plasma calcium than in normal parathyroid tissue.