Aliquots of the same serum sample from 10 proven and 10 probable cases of primary hyperparathyroidism (1 degree HPT) and 25 of hypercalcemia of malignancy (HCM) were sent to two different laboratories for C-terminal or midmolecule and N-terminal immunoreactive parathyroid hormone (iPTH) assays and total serum calcium measurements. Elevations in iPTH were observed in 70% to 95% of 1 degree HPT and 13% to 46% of HCM cases. There was a good correlation among the assays in the 1 degree HPT group. A significant correlation was found only between the C-terminal and N-terminal assays from the same laboratory in the HCM group. Only one (5%) of 20 1 degree HPT patients had normal iPTH in all assays while only one (4%) of 25 HCM patients had elevated iPTH in all assays. This study shows that currently available assays for iPTH can detect elevations in most patients with 1 degree HPT and can discriminate them from HCM. When renal function is impaired an N-terminal assay can still discriminate.