1. "Inactive" renin in human plasma can be revealed by pH 3.3- or cold-mediated activation and in normal plasma represented 76% of the "total" renin. 2. Pregnancy plasma contained considerably more "inactive" renin and consisted of 93% of "total" renin. 3. "Active" renin in normal plasma had an apparent molecular weight of 43,000 compared with 60,000 for "active" renin in pregnancy plasma by gel filtration. 4. "Inactive" renin in pregnancy plasma also had an apparent molecular weight of 60,000, while in normal plasma there were two peaks of inactive renin at 62,000 and 46,000. 5. After affinity chromatography of a protein preparation from pregnancy plasma on Concanavalin A-Sepharose activation by pH 3.3 could no longer be produced, suggesting that the activating factor had been removed, as would occur if it were not a glycoprotein. When pepsinogen, in a concentration similar to that found in plasma, was added prior to dialysis to pH 3.3 activation was restored. 6. Ion-exchange chromatography demonstrated that at pH 8.4 "inactive" renin bore slightly less negative charges than "active" renin. 7. "Inactive" renin in human plasma therefore appears to be a larger molecular weight species than the "active" renin in normal plasma and is capable of activation during treatment to pH 3.3 or cold with no apparent alteration in size. The results suggest an important role of pepsin (after conversion from pepsinogen) in the activation of "inactive" renin during dialysis at pH 3.3.