Abstract Disappearance of a renin inhibitor from the blood of nephrectomized animals has been postulated for many years. The observation that phospholipid renin preinhibitor concentration in canine blood did not fall within 48 hours of binephrectomy stimulated comparison of kidneys with other organs as sources of this compound. Its concentration in rat kidney and liver lipid was of the same order and significantly higher than in erythrocyte lipid. It also occurs in heart tissue. Coidentity of preinhibitor from different organs was determined by one and two dimensional thin layer chromatography (TLC) in several solvent systems and by assay of biological activity. The concentrations of preinhibitor in rat kidneys and livers, its R f by TLC, and the R f of its base moiety by paper chromatography suggest it is phosphatidyl ethanolamine but until the complete chemical structure in different tissues and species is clear, this phospholipid is described by its indirect biological effect on renin. Forty-eight hours after binephrectomy, total phospholipids in rat erythrocytes increased significantly without a parallel rise of preinhibitor as was observed previously in dogs. In plasma there was no change. Lipid from rat erythrocytes (high K +-low Na +) contained significantly higher concentrations of total phospholipids and preinhibitor than lipid from canine erythrocytes (high Na +-low K +). At least 75 per cent of canine erythrocyte preinhibitor is recoverable from stroma, suggesting it is mainly a membrane component. In very old rats, the phospholipid concentration in erythrocyte lipid was 69 per cent of normal, while preinhibitor and phosphatidyl serine were 21 and 35 per cent, respectively. Preinhibitor concentrations in renal tissue and lipid of old animals were also below normal. These deficiencies may be related to well-recognized changes in blood pressure and salt and water metabolism in old age.