In the largest reported family of patients with multiple endocrine neoplasia type 1 (MEN 1), hyperparathyroidism was expressed at first screening in 33 patients by elevation of ionized calcium (IC) (30 cases) or parathyroid hormone (three cases) without elevation of albumin-corrected total calcium (ACTC). Three of these 33 patients have shown a progressive rise in IC and later an elevation of ACTC. However, the age distribution suggests that in others the level of IC may remain stable at a minimally elevated level throughout life with ACTC remaining normal except for transient rises at the times of intercurrent illness or surgical operation. Even when ACTC is normal preoperatively, patients with an elevation of IC require radical subtotal parathyroidectomy or total parathyroidectomy and forearm implantation to restore IC to a normal level. Institutions that rely on ACTC as a screening test for hyperparathyroidism in MEN 1 will miss the diagnosis in nearly half of patients under the age of 30. The greatest deficiency in using ACTC occurs in the follow-up of patients who have undergone parathyroidectomy for MEN 1. Only three of 11 recurrences were evidenced by this measurement