The effects of calcium on parathyroid hormone (PTH) release were studied in vivo and in vitro in primary hyperparathyroidism (HPT) and in vitro in secondary HPT. In vivo the serum PTH was clearly reduced by intravenous calcium infusion in all the examined patients with primary HPT caused by adenoma. In vitro the release of PTH from dispersed parathyroid cells was likewise suppressed by raising the calcium concentrations in the incubation media, though in all cases a basal release of PTH still persisted even at high calcium concentrations. The degree of suppressibility in vitro varied, but in both primary HPT with adenoma and in secondary HPT it was inversely related to the patients' serum calcium values. These results suggest that the secretion of PTH in patients with primary and secondary HPT is not autonomous either in vivo or in vitro. Furthermore, the non-suppressible basal release of PTH indicates that a major cause for the increased secretion of PTH is the increased number of parenchymal cells. However, the degree of suppressibility of the individual cells rather than the absolute number of cells, seems to be of great importance for the individual serum calcium values in HPT.