Although elevated extracellular calcium concentrations inhibit PTH release, little is known about the necessity of extracellular calcium for the secretory process in this cell type. In the studies reported here, we examined the effects of low extracellular calcium concentrations on basal and agonist-stimulated immunoreactive PTH (iPTH) release in dispersed bovine parathyroid cells. There was a difference of 15% or less in the rate of iPTH release from cells exposed for 30-60 minutes to calcium concentrations varying from less than 10(-8) mol/L to 1 mmol/L. Low calcium concentrations likewise had no effect on dopamine-stimulated iPTH secretion. We employed high performance liquid chromatography (HPLC) to demonstrate directly that EGTA did not alter the degradation of PTH in the medium and that the release of intact PTH was stimulated slightly by very low extracellular calcium concentrations. Like iPTH release, both the basal and dopamine-stimulated cAMP content in parathyroid cells were unchanged by extracellular calcium concentrations as low as 10(-8) mol/L. Following exposure of cells to EGTA for two or more hours, there was a 50% to 60% inhibition of iPTH secretion. This reduction in secretory rate was not reversible, however, by the readdition of 0.1-1.0 mmol/L calcium for one hour. These results demonstrate that the secretion of PTH differs from that of many other exocytotic systems not only in that hormonal release is inhibited at high extracellular calcium concentrations but also in that extracellular calcium is not needed for acute hormonal release.