Renin secretion of rat kidney slices was studied as a function of extracellular K concentration. Independently of osmolality and extracellular Na and Cl concentrations, increasing K inhibited secretory rate in a concentration-dependent manner. At 60 mM K, rates were only a few per cent (1.6 +/- 0.8 and 3.5 +/- 0.5%, depending on Na and/or osmolality) of the rate measured at 4 mM K. Lowering extracellular Ca concentration from 2.65 X 10(-3) to less than 10(-8) M stimulated secretion and abolished the inhibitory effect of 60 mM K; these effects were reversible. Methoxy-verapamil and verapamil antagonized the inhibitory effect of 60 mM K in concentration-dependent manners; methoxy-verapamil was the more potent. Lowering Ca from 3.0 to 0.25 mM potentiated the antagonistic effects of both drugs. These results are consistent with the hypothesis that depolarization of juxtaglomerular cells opens voltage-sensitive Ca channels and that the influx of Ca mediates the inhibitory effect of depolarization on renin secretion. The results are consistent with the more general hypothesis that intracellular Ca plays an inhibitory coupling role in the control of renin secretion.