Intraoperative identification of abnormal parathyroid glands during initial neck exploration for primary hyperparathyroidism is challenging and may require extensive dissection of the neck and mediastinum. We, therefore, evaluated the impact of preoperative localization with Technetium-99m-sestamibi (Tc-99m-sestamibi) and Iodine-123 radionuclide subtraction imaging on operative time and success of initial operation for primary hyperparathyroidism. From January 1989 to September 1992, 42 patients underwent neck exploration for primary hyperparathyroidism; 21 patients underwent neck exploration without preoperative radionuclide scanning, and 21 patients were operated upon following radionuclide Tc-99m-sestamibi localization. In the control group, pathologic exam revealed 15 patients had solitary adenomas, and six patients had diffuse hyperplasia. In the Tc-99m-sestamibi group, 16 patients had solitary adenomas, four had diffuse hyperplasia, and one had multiple adenomas. Analysis of patient demographic data revealed no differences between the control group and the Tc-99m-sestamibi group in mean age (56 vs 59 years), mean intact PTH levels (249 vs 234 pg/mL), mean total calcium (11.3 vs 12.0 mg/dL), and mean ionized calcium (6.19 vs 6.28 mg/dL). Comparison of operative data revealed no differences between groups in the mean number of parathyroid glands identified and biopsied per patient (3.1 vs 3.3), the mean largest diameter of the resected adenomas (19.6 vs 20.0 mm), and the number of patients requiring thymectomy, thyroid resection, retroesophageal exploration, mediastinal exploration, or carotid sheath exploration. The operative success rate was 90 per cent for the control group versus 100 per cent for the Tc-99m-sestamibi group.(ABSTRACT TRUNCATED AT 250 WORDS)