Patients with diabetes generally exhibit normal plasma catecholamine responses to standing. Some have blunted norepinephrine responses and postural hypotension-hypoadrenergic postural hypotension due to classic diabetic adrenergic neuropathy. Others, including some with postural hypotension, have exaggerated norepinephrine responses to standing. In order to clarify the pathogenesis of this hyperadrenergic state which occurs in a subset of diabetic patients, we studied aldosterone secretion, vascular and metabolic responsiveness to the administration of norepinephrine, and intravascular volumes in four diabetic patients who were selected for their exaggerated plasma norepinephrine responses to standing. Three of the four patients also exhibited (hyperadrenergic) postural hypotension. None of the hyperadrenergic diabetic patients had evidence of hypoaldosteronism or vascular resistance to norepinephrine, but all four patients had subnormal red blood cell masses and the mean (±SE) red blood cell mass (13.1 ± 1.0 ml/kg) was approximately half of that of age- and sex-matched diabetic controls (26.5 ± 2.7 ml/kg, p < 0.01). Thus, intravascular volume contraction, specifically a reduction in the red blood cell mass, may play an important role in the pathogenesis of hyperadrenergic state observed in a subset of diabetic patients and in the pathogenesis of hyperadrenergic postural hypotension in affected diabetic patients.