Plasma renin activity (PRA) was studied in eight patients maintained on a 100 mEq sodium diet who had diabetes mellitus with orthostatic hypotension (OH) and in eight diabetic matched controls without orthostatic hypotension. Signs of neuropathy and nephropathy were more frequent in patients with OH. Supine PRA was 1.2 ± .2 ng./ml. (S.E.M.) in OH and 3.0 ± .9 in controls (P < .1). Following upright posture for one-half hour, patients with OH demonstrated a fall in mean blood pressure from 102 ± 8 mm. Hg. to 72 ± 8 (P < .001). Despite this stimulus for renin release, PRA was 1.5 ± .3, significantly lower than controls, 4.2 ± .8 (P < .01). In patients with OH, mean blood pressures remained lower after four hours of upright posture (80 ± 8) than supine (P < .005). PRA was 2.5 ± .6, again lower than in control diabetic patients (5.6 ± .9) (P < .02). These results contrast with those in ten out of fifteen reported cases of idiopathic orthostatic hypotension who demonstrated an increase in PRA to the stimulus of upright posture. One explanation for decreased renin release in diabetic patients with OH would be defective catecholamine stimulation. In one patient who was given infusions of norepinephrine for one-half hour on two successive days, no increase in PRA was observed. The associated nephropathy in diabetic patients with OH suggests the possibility of defective renal renin stores or renin releasing mechanisms. When combined with other possible defects in blood pressure homeostatic mechanisms such as catecholamine deficiencies and blood volume abnormalities, an inadequate response of the renin-angiotensin system may be etiologjcally related to the OH in patients with diabetes. DIABETES 23:835-40, October, 1974.Orthostatic hypotension with or without supine hypertension may be a severe and disabling complication of diabetes mellitus. The precise mechanisms reFrom the Joslin Clinic and the Elliott P. Joslin Research Laboratory Divisions of the Joslin Diabetes Foundation, and the