PRA, active renin, and inactive renin (IR; activated by dialysis to pH 3.3 and 7.4) were measured in the plasma of 53 patients with diabetes mellitus and 32 normal volunteers (group 1). Proteinuria was present in 21 diabetics (group 3; nephropathy) and absent in 32 diabetics (group 2). The mean PRA was lower in group 3 than in groups 1 and 2. PRA less than 0.2 ng/ml. h occurred more frequently and at a younger age i n uncomplicated diabetics than in normal controls. Despite very low PRA, plasma aldosterone was normal in most of the diabetics. IR was significantly higher than normal in the uncomplicated diabetics and was greatly increased in diabetics with nephropathy. Since the kidneys are a principal source of IR, and since patients with diabetic nephropathy have consistently elevated plasma IR, it is possible that increased plasma IR in patients without proteinuria or reduced renal function might be an early sign of renal involvement. However, as other explanations of increased plasma IR exist, the hypothesis must be tested by longitudinal studies of diabetic patients. (J Clin Endocrinol Metab56: 557, 1983)