There is a continual search for a better imaging modality for parathyroid pathology. In recent years, Tc-99m sestamibi has been proposed as an alternative to T1-201 for parathyroid scintigraphy. The purpose of this study is to assess the usefulness of a double-phase Tc-99m sestamibi SPECT technique for parathyroid imaging. Sixty-one consecutive patients with hyperparathyroidism were studied. Sixteen had previously undergone unsuccessful surgery for hyperparathyroidism. SPECT imaging of the neck and chest was performed at 15 minutes and again at 2 hours after 20-25 mCi of Tc-99m sestamibi was given intravenously. A positive scan was defined as a region of increased focal uptake that persisted on the delayed images. When compared with surgical findings, double-phase sestamibi SPECT correctly identified 55% (26/ 47) of the parathyroid adenomas in the previously unoperated group, and 91% (10/11) of the parathyroid adenomas in the reoperative group. Double-phase sestamibi SPECT was negative in 92% (109/118) of the normal parathyroid glands in the previously unoperated group, and in 88% (15/17) in the reoperative group. These preliminary data suggest that double-phase Tc-99m sestamibi SPECT is a promising procedure for the preoperative detection and localization of hyperfunctioning parathyroid tissue, especially in patients with recurrent or persistent postoperative hyperparathyroidism.