Renin release from the juxtaglomerular cell appears to be inversely related to calcium concentration. We studied the role of Ca⁺² to confirm recent findings and to further explore the role of intracellular calcium as well as the calciumcalmodulin system in renin release. A rat renal cortical slice preparation was used. Isoproterenol (10⁻⁶m) caused significant stimulation of renin release, whereas angiotensin (All; 5 × 10⁻⁵m) suppressed basal as well as isoproterenol-stimulated renin release. Removal of calcium from the buffer reversed All suppression of renin release. Nifedipine (10⁻⁵m), a specific calcium channel blocker, induced a marked increase in basal renin release. TMB-8, an inhibitor of intracellular calcium release, also caused a dose-related increase in basal renin release. The calmodulin antagonists trifluoperazine and calmidazolium both caused significant dose-related increases; however, calmidazolium was a more potent stimulator. Low extracellular calcium or nifedipine concentrations did not alter isoproterenol-induced renin release. Isoproterenol further stimulated renin release in the presence of trifluoperazine and calmidazolium. These results suggest that acute β-adrenergic stimulation of renin in independent of changes in levels of extracellular and intracellular calcium and calmodulin. These studies provide further evidence that unlike most other secretory systems, the reduction of intracellular calcium or inhibition of the calcium-calmodulin system in the juxtaglomerular cells of the kidney acts as a secretogogue. (Endocrinology117: 601–606, 1985)