OBJECTIVE Because of an overlap between serum PTH values in healthy controls and hyperparathyroid patients we sought to evaluate a short stimulation and suppression test for differentiating the two groups. METHODS Subjects were 34 patients with primary hyperparathyroidism (PHPT) and 25 healthy controls. METHODS After stimulation with intravenous EDTA (10 mg/kg body weight in 5 minutes) blood samples were obtained for up to 15 minutes. After an oral calcium dose of 1 g, blood samples were obtained at 1 and 2 hours. After an intravenous calcium dose (2.5 mg/kg body weight in 30 seconds), blood samples were obtained serially for 20 minutes. METHODS Serum PTH(1-84) was measured by a double antibody technique. RESULTS The intravenous EDTA test resulted in an average 2.6-fold increase of serum PTH(1-84) in hyperparathyroid patients, whereas it increased 10.5-fold in controls. A response was absent in three of 23 patients. There was an overlap in results between patients with mild hyperparathyroidism and controls. The oral calcium dose decreased serum PTH(1-84) in patients to 0.73 and in controls to 0.55 of the basal value, but six of 15 patients and two of 12 controls did not respond. The intravenous calcium test resulted in a drop of serum PTH(1-84) in hyperparathyroid patients to 0.51 and in control subjects to 0.40 of the basal value, and non-responders were not observed. There was a strong correlation between the responses to the EDTA and the calcium infusion tests in the patients (r = 0.97, P less than 0.01). Fasting serum calcium and serum PTH(1-84) showed a positive correlation in PHPT patients (r = 0.75, P less than 0.001) and a negative correlation in control subjects (r = -0.41, P less than 0.05). Based on these relationships, hyperparathyroid patients and controls could be completely separated. CONCLUSIONS The wide range of responses to stimulation and suppression tests and the correlation between these responses in hyperparathyroid patients indicate various degrees of autonomy. As the response to these tests is less marked in patients than in controls and both groups still overlap, these tests are not useful for the diagnosis of primary hyperparathyroidism.