Plasma renin exists in an active form or as an inactive zymogen that resembles a prorenin present in homogenates of human kidneys. We examined the relation of diabetes and its microvascular complications with the level of plasma inactive renin activated by dialysis to pH 3.3. Plasma inactive renin was measured in 235 diabetic patients and 90 nondiabetic controls. In the controls, the level of plasma inactive renin increased slightly with age but was never above 50 ng per milliliter per hour. In young diabetic patients studied within three years of the onset of diabetes the concentration of inactive renin was normal, and in some older diabetics without complications it remained within the age-adjusted normal range for many years. However, in patients with retinopathy or albuminuria, plasma inactive renin was above the normal range with few exceptions, reaching levels 50 to 200 per cent above the upper limits of normal in patients with nephropathy. The frequency of neuropathy was also significantly higher among patients with levels above the normal range. In 37 per cent of the diabetics followed during one to three years of conventional treatment, plasma inactive renin increased significantly, but in another group of diabetics under intensive treatment, the level rose in only 7 per cent and fell in 43 per cent. We conclude that there is a close association between a high level of plasma inactive renin and the presence of microvascular complications, and that the level of inactive renin can be modified by intensive treatment of diabetes.