Plasma active and acid activated inactive renin was measured in healthy subjects and in patients with diabetes mellitus. The angiotensin I generated from the incubation of non-acidified plasma with pig renin substrate was expressed as total renin concentration (PRC) and that from acidified plasma was expressed as total renin concentration (TRC). The inactive renin concentration (IRC) was calculated as TRC minus PRC. With regard to plasma renin activity (PRA) and PRC, no significant difference was found between normal and diabetic groups. TRC and IRC in diabetics with no clinical sign of microangiopathy were 22.8 .+-. 1.7 and 15.2 .+-. 1.3 ng/ml per h (mean .+-. SE), and these values were not significantly different from those in the healthy subjects (20.5 .+-. 1.5 and 13.2 .+-. 1.5 ng/ml per h). However, TRC and IRC in diabetics with retinopathy and clinical nephropathy was 38.8 .+-. 3.4 and 30.7 .+-. 3.2 ng/ml per h, and these values were significantly higher than those in the above 2 groups, respectively. Moreover TRC and IRC in diabetics with retinopathy and no clinical nephropathy were 33.8 .+-. 5.7 and 24.9 .+-. 5.5 ng/ml per h, and these values were significantly higher than those in the control group. IRC was not significantly correlated with fasting blood sugar and mean blood pressure levels, however a significant correlation was found between IRC and BUN [blood urea nitrogen], and IRC and P.S.P. [phenolsulfonphthalein] excretion in 15 min. Increased inactive renin in diabetes mellitus may be related to the progression of the renal lesions associated with diabetic microangiopathy.