SUMMARY Plasma membrane (PM) and endoplasmic reticulum (ER) enriched fractions were isolated from the homogenized rat kidney. Transmission electron micrographs of PM showed empty vesicles but no granules present in the fraction. Kallikrein activity was detected in the homogenate, microsomal, and PM and ER fractions; it was most enriched in PM fraction. PM-kallikrein released a klnin, cleaved the peptide substrate, S-2266, and a radiolabeled arginine ester. The ester was also hydrolyzed by renal enzymes other than kallikrein. PM-kallikrein was activated by Triton X-100, phospbolipase A, lysolecithin, and by a peptide, melittin. Melittin (2 fiM) was most potent; it increased the activity to 750%. Solubilized PM and ER kallikrein were inhibited by antibody to rat urinary kallikrein, but membrane-bound kallikrein was more resistant to inhibition. The Km of S-2266 was higher with renal than with urinary kallikrein. The PM and ER fractions also contained renin. Renin activity was enhanced 30-fold or more by activators of kallikrein, e.g., by phospholipase A, lysolecithin, and melittin. Low sodium diet increased the activity of kallikrein in the homogenate and in the membrane fraction. This diet increased the activity of renin in the homogenate but not in the membrane fraction. It is suggested that prekallikrein is on PM and is activated prior to release from the membrane. Membrane-bound renin may be a form of renin retained in the kidney.