Primary hyperparathyroidism, although often silent clinically, may lead to significant morbidity if it remains untreated. In more than 95% of all cases the cause is a parathyroid adenoma or glandular hyperplasia. Regression of disease follows successful surgical excision of the abnormal parathyroid gland. Recurrent or persistent hyperparathyroidism is most commonly caused by solitary adenomas, which may have an ectopic location. Preoperative localization of lesions may improve postoperative cure rates and decrease morbidity. Thallium T1 201 chloride-technetium Tc 99m pertechnetate subtraction scintigraphy was performed on 15 patients with primary hyperparathyroidism. The sensitivity and specificity for detection of abnormal glands were 90% and 95%, respectively. False-positive or false-negative results were minimize by strict adherence to a protocol and by the use of well-defined diagnostic criteria. Because of the superior sensitivity and specificity, this modality should be the primary imaging method of choice for preoperative evaluation of primary hyperparathyroidism. The relative role of other imaging modalities is also discussed.