Ninety-five percent of primary hyperparathyroidism is caused by either a solitary hyperfunctioning adenoma or chief cell hyperplasia. While there is a great deal of variation in the location of the parathyroid glands, 90-95% of all abnormal parathyroid tissue will be identified at initial exploration regardless of the preoperative localization procedure. Adenomas not identified at initial exploration are likely to be ectopic. Reexploration is a difficult and time-consuming procedure. The challenge, therefore, is to develop a reliable, noninvasive test that will locate aberrant parathyroid tissue preoperatively with the goal of simplifying the surgical procedure and reducing the incidence of reexploration. A radiopharmaceutical which localizes selectively in parathyroid tissue would be ideal. Currently, no single radiopharmaceutical is adequate. Recently, dual isotope subtraction scintigraphy using T1-201 chloride and Tc-99m pertechnetate has yielded promising results. The authors have investigated this procedure in 42 patients, 25 of whom to date have had surgical exploration. Of the 25 adenomas or focal hyperplasia sites found at surgery, 23 (92%) were correctly located preoperatively. There were two false-negative sites and five false-positive sites. The purpose of this paper is not only to describe the methods used and results obtained but also to discuss the merits and limitations of the technique in comparison with other imaging modalities so that its role, in today's climate of cost containment, may better be defined.