The experience of the surgeon and precise localization of abnormal parathyroid glands determine the success of surgery for primary hyperparathyroidism (HPT). In HPT patients undergoing repeat surgery, the use of localization studies improved the ability to identify the remaining abnormal parathyroid tissue. This study investigated the roles of preoperative localization techniques for initial surgery for primary HPT. From 1985 through 1997, two noninvasive localization procedures, ultrasonography (US) and 201thallium chloride-99mtechnetium pertechnetate subtraction scanning (Tl-Tc), were used prior to initial exploration for primary HPT in 76 patients. Their accuracy was determined on the basis of surgical and pathologic results. The surgical success rate was 96% (73/76). The sensitivities of US and Tl-Tc were 71% and 49%, respectively. The sensitivity of Tl-Tc was higher for the lower parathyroid glands. In 21 of 26 patients who underwent fine-needle aspiration (FNA) of the suspected enlarged parathyroid gland, the diagnosis of parathyroid adenoma was confirmed preoperatively. We conclude that the concomitant use of US and FNA is a safe and convenient method for preoperative localization of the parathyroid glands prior to initial surgical exploration in patients with primary HPT. Bilateral neck exploration by an experienced surgeon should be the routine procedure. US and Tl-Tc alone offer limited localization information, and unilateral exploration should be reserved for selected cases in which the results of these two imaging studies are consistent with one another.