The effects of removing external calcium and inhibiting entry of calcium into the cell by treatment with D-600 on renin release from renal cortical slices of male Sprague-Dawley rats were examined. Baseline renin release, angiotensin II (All)-induced inhibition, and isoproterenol-induced stimulation of renin release were studied. Removal of external calcium by chelation with 5 mM EGTA inhibited basal renin release while treatment with 1 mM EGTA stimulated basal renin release slightly. Incubation of slices with zero calcium medium containing 1 mM EGTA had no effect on isoproterenolinduced stimulation of renin release. In contrast, similar treatment reduced the inhibitory effect of AH from 58.7% of baseline to 85.3% (p < 0.001). Similarly, blockage of calcium entry into cells with D-600 had no effect on isoproterenol-induced stimulation of renin release but abolished All-induced inhibition. Replacement of sodium in the bathing medium with choline had no effect on baseline renin release or on All-induced inhibition of renin release, ruling out the possibility that D-600 altered renin release via an effect on sodium influx. Taken together, the data strongly suggest that All-induced inhibition of renin release is partially dependent on the presence of external calcium but that isoproterenol- induced stimulation of renin release is not. © 1982 American Heart Association, Inc.