Unilateral neck exploration (UNE) is a controversial approach to the treatment of primary hyperparathyroidism (PHP), and most surgeons favor bilateral neck exploration. The aim of this study was to assess the value of ultrasonography, sestamibi scintigraphy, and intraoperative measurement of urinary cyclic AMP (UcAMP) or 1-84 PTH in 200 patients undergoing unilateral neck exploration under local anesthesia. Conditions for UNE were (1) a presumed solitary adenoma detected by ultrasonography, (2) no thyroid disease, and (3) no family history of PHP or multiple endocrine neoplasia. Patient's consent was obtained for conversion to bilateral exploration according to surgical and biologic findings. Sensitivity of ultrasonography was 92.5%. Sestamibi scintigraphy, performed in 70 patients, was less sensitive than ultrasonography (80%). Persistent PHP was accurately detected by intraoperative measurement of UcAMP or 1-84 PTH in all cases. At follow-up, 96.0% of the patients were cured either after unilateral neck exploration only (90.5%), or after conversion into bilateral exploration. Ultrasonography and intraoperative measurement of 1-84 PTH allow unilateral neck exploration with excellent results in a selected group of patients with PHP.