The present study was carried out to determine the effect of lipid peroxidation on renin release from renin granules of the rat. Renin granules were isolated from the kidney cortex by discontinuous sucrose density gradient centrifugation. Renin acitivity was measured by radioimmunoassay and lipid peroxidation was estimated by means of the thiobarbituric acid test. Renin release from isolated renin granules was markedly stimulated by incubation at 37°C in the presence of ascorbic acid or ferrous ions, accompanied by increased formation of lipid peroxide in renin granules. These simultaneous increases in lipid peroxidation and renin release were abolished by the addition of N, N'-diphenyl-p-phenylenediamine. On the other hand, dehydroascorbic acid or ferric ions caused no change in lipid peroxidation and renin release. In addition, the molecular weight of renin released from the granules was 40000 and its activity was not changed after acidification. From these findings, it is assumed that ascorbic acid and ferrous ions stimulate the peroxidation of endogenous lipids that form part of the membrane of renin granules, and this process results in a breakdown of renin granules.