Autonomic nervous system dysfunction has been described frequently in uremic patients. The purpose of this study is to determine the localization of this abnormality and to study the possible relationship between autonomic dysfunction and the occurrence of dialysis hypotension. Sixteen consecutive patients participated in the study, 5 of whom had a history of dialysis-induced hypotension. These 5 patients were compared to the other 11 as regards the cardiovascular response to isoproterenol infusion, tilt test and arteriovenous (AV) fistula occlusion. None of the responses to the above mentioned stimuli was significantly different between the 2 groups. In the whole study population, an index of parasympathetic control of heart rate (variation of heart period, VHP) was reduced (31 ± 5 vs. 59 ± 9 ms in age-matched controls; p < 0.025). Heart rate and diastolic blood pressure response to isoproterenol infusion was normal (+23 ± 2 beats/min and -9 ± 3 mm Hg; p < 0.005 for both), indicating normal response of effector organs to beta-adrenergic agonist stimulation. Similarly, plasma norepinephrine increased significantly (+294 ± 51 pg/ml; p = NS from normal laboratory values) in response to head-up tilt, and heart rate increased simultaneously in all but 5 patients. Blood pressure response was within normal after 10 min of head-up tilt at 60° in all but 3 patients; only 1 of these 3 patients was in the group of dialysis hypotension. However, during AV fistula occlusion, heart rate did not change markedly, despite the significant increase in systolic blood pressure, suggesting an altered sensitivity of baroreceptor reflex arc. Since VHP was abnormal, the possibility exists that the blunted response of heart rate during AV fistula occlusion was due to impaired efferent rather than afferent vagal pathway of the baroreflex arc. The present study indicates that autonomic nervous system dysfunction in hemodialysis patients involves cardiac efferent parasympathetic pathway whereas adrenergic responses are within normal. These findings could not explain the occurrence of dialysis hypotension in this population. The latter is probably due to hemodynamic fa