Gel filtration of normal mouse serum revealed the presence of high molecular-weight forms of renin, in addition to the well-recognized 40 000 dalton form. The distribution of renin was measured by using both the antibody trapping method, which measures renin's enzymatic reactivity, and by a direct radio-immunoassay, which detects the renin molecule by its antigenic properties. A well characterized and distinct peak corresponding to a molecular weight of 200 000 or greater was always present. A less distinct peak was seen between 70 000 and 140 000 daltons. The well separated and symmetrical peak at 40 000-45 000 daltons was secreted from both kidneys and submaxillary glands and disappeared almost completely after combined nephrectomy and sialoadenectomy in contrast to the forms of higher molecular weight. The higher the molecular weight the lower was the specific enzymatic reactivity found to be. The 200 000-dalton peak was mainly detectable by the direct assay, although it was demonstrated to contain enzymatic reactivity to a small extent. The 40 000-dalton peak had a specific enzymatic reactivity and molecular weight identical to that of pure submaxillary renin.