Oxyphil cell function in secondary parathyroid hyperplasia due to chronic renal failure was evaluated using in situ hybridization and heterotransplantation of parathyroid tissue. In situ hybridization and histologic analysis were performed on continuous frozen sections using 22 parathyroid tissues. A restricted area composed exclusively of oxyphil cells was observed in 10 specimens, and an area of only chief cells was found in 12 specimens. Silver grains demonstrating the existence of parathyroid hormone (PTH) mRNA were 18.8 ± 7.8 (mean ± SD) in oxyphil cells while those in chief cells were 17.2 ± 7.5. PTH mRNA was abundant in both the oxyphil and chief cells. Further analysis of oxyphil cell function was assessed by the heterotransplantation of parathyroid nodules, consisting exclusively of oxyphil or chief cells, into nude mice. The function of these implants was assessed by measuring the concentration of human intact PTH which did not cross-react with mouse PTH. Serum PTH concentrations were correlated with the volume of implanted tissue. Elevations of PTH concentrations were similar in the mice transplanted with oxyphil or chief cells, indicating that both cell types had similar PTH secretory activity. The basic histologic characteristics of both cell types were not altered following transplantation. These results demonstrate that oxyphil cells in secondary parathyroid hyperplasia synthesize and secrete PTH, and that this secretion contributes to the pathophysiology of hyperparathyroidism.