We investigated cyclooxygenase expression in parathyroid glands from patients with various pathological conditions in order to coordinate levels of immunoreactivity with histology, with preoperative serum levels of calcium, phosphate, and intact parathyroid hormone, and with clinical diagnoses. Surgical specimens were obtained from 38 patients diagnosed with adenoma and primary, secondary, and tertiary hyperplasias. Incidentally removed parathyroids served as controls. After routine histological processing, approximations of total area and area of oncocytic nodules were calculated for each section of gland. Immunohistochemical reactivities for Cox-1, Cox-2, and values for integrated Cox-2 reactivity were quantified and compared with the clinical diagnoses and preoperative serum biochemistry. For the pooled cases, serum phosphate and PTH were directly related to each other, to total glandular area, and to integrated oncocytic area. Serum calcium was inversely related to serum phosphate and PTH levels as well as to total gland size. Within the adenoma group, the pure chief cell adenoma patients were younger and their tumors showed greater proliferative activity than those in the oncocytic adenoma group. For secondary and tertiary hyperplasias, the number of oncocytic nodules was significantly higher than in the adenomas and primary hyperplasias. In our study, the oncocytic cells are the only demonstrable site of Cox activity. It is suggested that the oncocytic cells play a role in prostaglandin metabolism within the parathyroids and may have a role in the regulation of PTH secretion.