The study was designed to characterize L-[methyl-11 C]methionine accumulation in abnormal parathyroid tissues of hyperparathyroidism (HPT). METHODS Thirty-four patients with primary (n = 32) or secondary HPT were investigated with PET before primary or reoperative (n = 25) parathyroid surgery. Parathyroid 11C-methionine accumulation was analyzed for integrated uptake values in defined tissue volumes standardized for the injected dose and body weight (SUV), four contiguous pixels of maximal accumulation (SUVhs), SUV multiplied by area of region of interest (SUVr) and by the excised tissue weight (SUVw). Transport rate constants (slope, slopehs) were calculated according to Patlak's formula using plasma 11C activity corrected for 11C-methionine metabolites. RESULTS True-positive localization was achieved in 85% of patients in whom 81% of the excised parathyroid lesions were visualized; no false-positive results were obtained. Corresponding proportions were 59% and 57% for CT and 55% and 52% for ultrasound, respectively. In the true-positive cases, parathyroid SUV, SUVhs and transport rate constants were consistently higher (p < 0.01) than in the thyroid, pharynx-esophagus, neck muscle and apical lung. Parathyroid SUV, SUVhs and SUVr increased with intact serum parathyroid hormone and calcium values (p = 0.0001-0.031), and weight of the excised tissue correlated with SUV and SUVhs (p = 0.024, 0.044). Parathyroid SUVhs varied strongly with the transport rate constants (p = 0.0008), and SUVr as well as s-calcium values differed significantly between parathyroid adenomas (n = 11), chief cell hyperplasias (n = 13), inadvertent implants (n = 3) and parathyroid cancers (n = 3). CONCLUSIONS Carbon-11-methionine PET has potential application in preoperative localization and metabolic characterization of abnormal parathyroid tissues in human HPT.