Plasma levels of intact parathyroid hormone (PTH) were measured intraoperatively before and after removal of one enlarged gland in 20 hyperparathyroid patients. In 13 patients with a single parathyroid adenoma, plasma levels of intact PTH-(1-84) had declined at 15 min after removal of the adenoma by 86.5 +/- 4.4% of baseline in the antecubital vein and by 85.6 +/- 4.2% in the ipsilateral internal jugular vein. In seven patients with parathyroid hyperplasia, the corresponding figures for decline at 15 min after removal of one enlarged parathyroid gland were only 26.6 +/- 6.4% and 7.8 +/- 29.4%. The fall in PTH levels was significantly less in hyperplasia than in adenoma (p less than 0.001). Thus 15 min after removal of one enlarged parathyroid gland, the decline in plasma level of intact PTH may distinguish between single adenoma and multiglandular disease as the cause of hyperparathyroidism.