The sympathetic nervous system is of major importance in the regulation of numerous physiological functions. While it is clearly established that there is a decreased noradrenergic status in people with autonomic neuropathy, the epinephrine secretion is much more controversial. Basal and mental stress-stimulated plasma catecholamine levels were measured in 42 diabetic patients with and without pathological cardiovascular function tests and in 13 healthy, non-diabetic control subjects. In addition, the excretion of catecholamines was measured in a 24 h urine collection and compared with the stress stimulated plasma levels. During mental stress exposure a diminished epinephrine secretion was found in diabetic patients with autonomic neuropathy compared with diabetic patients without neuropathy and the healthy control group (p < 0.05: respectively). The decreased epinephrine response to mental stress was strongly correlated with a diminished urinary excretion of this "neurotransmitter' (r = 0.46; p < 0.01). Diabetic patients suffering from cardiovascular autonomic neuropathy exhibit a diminished sympatho-adrenal response following mental stress exposure. Both measurement of urinary and mental stress stimulated plasma epinephrine levels following mental stress provide reliable information regarding sympatho-adrenal activity in diabetic patients.