Previous studies in the rabbit suggest resistance to parathyroid hormone (PTH) despite the reported presence of PTH-sensitive adenylate cyclase activity in renal cortical slices and tubules. The lack of response may reflect difficulties with complete parathyroidectomy in this species, which has been reported to possess 32 accessory glands. Aided by systematic histology of tissues extirpated during exploration, we tested the hypothesis that the rabbit possesses only four functional parathyroid glands and that the rabbit kidney is sensitive to the expected physiological actions of endogenous PTH. In all rabbits studied, only four glands could be identified histologically, two within the thyroids and two located in the fascial plane between the sternohyoid and sternothyroid muscles and the carotid artery. Surgical thyroparathyroidectomy markedly reduced serum Ca (6.3 vs. 10.6 mg/dl in sham-operated controls), increased the clearance (C) (3.51 vs. 0.78 ml/min) and fractional excretion (FE) of Ca (44.5 vs. 8.3%) while decreasing CP (1.14 vs. 2.40 ml/min), FEP (14.8 vs. 29.9%) and adenosine 3',5'-cyclic monophosphate (cAMP) excretion (341 vs. 760 pmol/min). These findings demonstrate the feasibility of using the described techniques for complete parathyroidectomy in the rabbit. Furthermore, they document the presence of only four functioning parathyroid glands and the renal sensitivity to endogenous PTH in this species.