Autonomic neuropathy is one of the complications of diabetes. Recently, several authors reported that measuring R-R interval variation of ECG is a noninvasive and useful method for testing parasympathetic function. However, there were few reports about sympathetic function in diabetics. In order to evaluate sympathetic function in diabetics quantitatively, we studied the responses of plasma norepinephrine (NE), epinephrine (E) and related factors after 60 min bed rest and sequentially during 10 min of upright posture and 5 min handgrip while still upright. We also studied the responses of NE and E during 5 min smoking in supine position. Subjects were divided into four age-matched groups. These were 15 normal subjects (Group I), 20 diabetics without complications (Group II), 20 diabetics with peripheral neuropathy but no autonomic symptoms (Group III) and 15 diabetics with autonomic symptoms (Group IV). We also studied R-R interval variation (CV: Coefficient of Variation) as a parameter of parasympathetic function and compared this with sympathetic function. Upon standing, blood pressure (BP) dropped precipitously in Group IV, whereas no significant changes were observed in the other three groups. Heart rate (HR) increased in Groups I and II, but not in Groups III and IV. During handgrip, BP and HR did not change significantly in all groups. Basal NE levels in Group IV were significantly smaller than those in Group I. NE responses to both standing and handgrip stimuli were markedly reduced in Group IV and, even in Group III, increments were significantly smaller than those in Groups I and II. Basal E levels did not differ, and significant changes were not observed after standing and handgrip in all groups. Both plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) in Groups III and IV were lower than those in Groups I and II at rest and standing. After smoking, both BP and HR increased significantly in Groups I, II and III, whereas no changes were observed in Group IV. Both NE and E responses were markedly reduced in Group IV and, even in Group III, responses were significantly smaller than those in Groups I and II. CV in Groups III and IV were significantly smaller than those in Groups I and II. In diabetics, CV was strongly correlated with NE increments after standing (r = 0.78, p less than 0.01). Also, CV was correlated with both NE and E increments after smoking (r = 0.71 (NE), r = 0.82 (E), p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)