Utilizing primary cultures of mouse renal juxtaglomerular cells we found that renin secretion during 20 h of incubation was stimulated by 100% when extracellular calcium was lowered from a basal level of 0.5 mM to below 1 microM, and was enhanced in a concentration-dependent fashion by 600% when extracellular calcium was increased up to 10 mM. The stimulatory effect of low calcium on renin secretion was apparent after the first hour of incubation, whereas the stimulatory effect of increased calcium occurred with a delay of at least 1 h. During the first hour of incubation increased extracellular calcium blunted the stimulation of renin secretion induced by forskolin (10 microM). The stimulatory effect of increased calcium was attenuated in the presence of 8-pCPT-cGMP, a membrane-permeable cGMP analogue, and in the presence of 100 mM sucrose. The stimulatory effect of increased calcium was blunted in the presence of 0.5 mM cobalt, which itself stimulated renin secretion at normal (0.5 mM) calcium concentrations. Renin synthesis by the cultured cells at low calcium was markedly attenuated in proportion with total protein synthesis, whereas renin synthesis was not altered at increased calcium concentrations. Our findings suggest that a rise of intracellular calcium, induced by an increase of extracellular calcium, is associated with a transient inhibition followed by a marked and regulatable stimulation of renin secretion. Neither calcium depletion nor calcium elevation appears to exert specific effects on renin synthesis in juxtaglomerular cells.