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1. The effects of calcium deprivation and D600 on the rate of renin release and seasonal variations in the response were studied on juxtaglomerular cells from a preparation of isolated rat glomeruli superfused in vitro. 2. Reduction of superfusate calcium concentration caused an increase in renin release, which was significantly higher during the summer (May-August) than during the rest of the year. 3. Addition of D600 (2 X 10(-4) M) to a calcium-free medium in the low responsive period caused a markedly increased renin release. In the high responsive period renin release increased more rapidly and to a higher level initially than observed in the control lines without D600. 4. It is suggested that the effect of calcium on renin release predominantly is mediated by changes in calcium bound to the plasma membrane of the juxtaglomerular cell. The sensitivity of this cell to changes in the extracellular calcium concentration seems to be regulated and varies with season, possibly due to regulation of the amount of calcium bound to the membrane.