Isolated cat kidneys were perfused in situ with Locke solution and renin release in response to isoprenaline was studied. Perfusion with isoprenaline produced a concentration-dependent enhancement of renin secretion. Increasing the concentration of stimulant also prolonged the duration of the secretory response. After a 10 min exposure to isoprenaline (0.3 .mu.M), there was a rapid facilitation of renin release which diminshed after 10-30 min, followed by a 2nd transient increase which declined over the next 40-60 min. Cycloheximide did not prevent augmented release when added together with the isoprenaline but did produce a reversible inhibition of the late phase when added 10 min after the isoprenaline. Omission of Ca from the perfusion medium failed to depress the renin release induced by isoprenaline, glucagon, or furosemide. During prolonged Ca deprivation, the cycloheximide-sensitive phase of isoprenaline-evoked release was depressed. The Ca antagonist D-600 [verapamil] failed to block the early phase of isoprenaline-induced renin secretion but inhibited the late phase of secretion. Ca alone elicited an explosive discharge of renin when added after a prolonged period of Ca free perfusion. These results support the view that extracellular Ca does not play an essential role in the mechanism of renin secretion from the renal juxtaglomerular cells, but an increased influx of this cation is needed for synthesis and/or mobilization of the enzyme. It is tentatively proposed that the release of Ca from intracellular storage sites may be the signal which triggers renin secretion.