1,25-Dihydroxycholecalciferol [1,25(OH)2D], besides its role in calcium and phosphorus homeostasis, is also an important immunoregulatory molecule. Plasma levels of this hormone may be normal or elevated in patients with primary hyperparathyroidism. 1,25(OH)2D has been reported to inhibit production of the cytokines interleukin-2 (IL-2) and IL-6. In the present study, we examined the effect of parathyroid adenoma excision on serum IL-2 receptor (IL-2R) levels and the release and production of IL-2R and IL-6 by peripheral blood lymphocytes (each measurement was performed twice). Ten patients (5 females and 5 males aged 45 to 78 years) with primary hyperparathyroidism were enrolled in the study. The diagnosis of primary hyperparathyroidism was based on the presence of asymptomatic hypercalcemia, hypophosphatemia, and elevated serum intact PTH levels. Three weeks after removal of the parathyroid adenoma, there was a significant increase in the serum level of IL-2R, as well as the PHA-stimulated peripheral blood lymphocyte production of IL-6 and release of IL-2R. The results indicate that the removal of a parathyroid adenoma in patients with primary hyperparathyroidism causes a significant increase in IL-2R and IL-6 levels. The mechanism by which hyperparathyroidism may affect these cytokines and how they seem related to the levels of vitamin D is discussed.