The efficiency of preoperative radioactive toluidine blue (RTB) scintigraphy for the localization of parathyroid pathology was evaluated prospectively in 69 patients (age range, 15 to 81 years; mean, 56 years) with primary hyperparathyroidism. Four patients have previously undergone negative exploratory surgery. Patients underwent preoperative dual radionuclide parathyroid-RTB/technetium 99m (Tc 99m)-thyroid scintigraphies with a computer-interfaced gamma-camera with a pinhole collimator. Computer-acquired scintigraphic data were analyzed for parathyroid localizations by an RTB-parathyroid/thyroid superposition technique. At surgery, parathyroid adenomas were found in 64 patients (single adenomas in 60 patients; two adenomas in four patients), nine of these adenomas were mediastinal. Four patients had parathyroid hyperplasia. One patient had no parathyroid pathology (negative exploratory surgery). Correlation between the surgical-pathologic findings and the scintigraphic RTB localization studies disclosed a sensitivity of 87%, with a specificity of 94%, and an overall accuracy of 92%. The routine use of preoperative scintigraphic parathyroid-RTB/Tc 99m-thyroid localization has proved to be highly effective, enabling detection of small hyperfunctioning parathyroid glands in normal and ectopic locations in a wide range of weights. In this series a success rate of 98% was achieved on initial and reexploratory surgery for primary hyperparathyroidism.