PRA, active renin, and prorenin were measured in 32 normotensive diabetic patients and 14 normal subjects of similar ages before and after iv injection of 40 mg furosemide. The majority of the diabetic patients had normal PRA and active renin levels before and after furosemide, but in 4 normal subjects and 5 diabetic patients PRA did not rise after furose-mide treatment to at least 0.25 ng angiotensin I/(L·s) as previously found in 90% of normal subjects. Two thirds of the diabetic patients had higher plasma prorenin levels than the normal subjects, and the mean increase in plasma prorenin after furo-semide was higher in the diabetic patients than in the normal subjects. Four of the 5 diabetic patients whose PRA failed to rise to the usual level after furosemide treatment attained a plasma prorenin level higher than any normal subject, suggesting that furosemide stimulated synthesis and secretion of prorenin, but that conversion of prorenin to active renin was impaired. These 5 diabetic patients also had higher plasma creatinine and potassium levels as well as an increased frequency of albuminuria compared with the other diabetic patients. In contrast, the 4 normal subjects whose PRA failed to reach the usual level after furosemide treatment had low unresponsive prorenin levels, indicating that furosemide did not evoke the expected increase in prorenin or renin synthesis. We conclude that the inability of some diabetic patients to increase PRA after furosemide treatment is not dependent on failure of renin synthesis, but reflects an impairment of the normal processing of prorenin, leading to high levels of prorenin in plasma.