SUMMARY1. These studies were conducted in isolated perfused rat kidneys to determine the influence of perfusion pressure, isoprenaline, K, and Na on renin release stimulated by acute Ca deprivation.2. Removing Ca from the perfusion medium for 10 min stimulated renin release and reintroducing Ca returned it toward control values.3. Lowering concentration of Ca in the perfusion medium from 5 to 0 mM increased the effectiveness of low perfusion pressure (50 mmHg) and isoprenaline (2.43 /SM) in stimulating renin release.4. At higher perfusion pressure (150 mmHg), renin release was inhibited in perfusion medium containing 2*5 mM-Ca but not in medium containing no Ca. In fact, high perfusion pressure stimulated renin release when the perfusion medium was without Ca.5. Raising concentration of K in the perfusion medium partially inhibited the renin release induced by Ca deprivation. Adding 5 mM-EGTA to Ca-deprived medium stimulated a greater rate of renin release than that of Ca-deprived medium alone. This greater renin release was also partially inhibited by raising K concentration in the perfusion medium.6. Lowering concentration of Na in the perfusion medium from 145 to 25 mm partially inhibited the renin release induced by Ca deprivation in the presence of low perfusion pressure or isoprenaline.7. These findings support the hypothesis that a decreased concentration of Ca in the cytoplasm of the juxtaglomerular cell stimulates renin release and increased Ca inhibits renin release. The sequence of events which leads to changes in cytoplasmic Ca might depend on the concentration of Ca in the perfusion medium, the renal perfusion pressure, the membrane potential of the juxtaglomerular cells, and Ca-Na exchange mechanisms.