Uncomplicated insulin-dependent diabetes mellitus (IDDM) is associated with a suppressed reflex response to sympathetic nervous system (SNS) stimulation and an enhanced pressor response to catecholamines. This study examined the SNS in subjects with IDDM (duration < 5 yr, n = 9) to determine the responsible mechanism within the cardiopulmonary baroreflex arc and the role played by extracellular fluid volume (ECFV) expansion. The reflex arc was tested by examining the plasma norepinephrine (PNE) and forearm vascular (FVR) responses to 60 min of cardiopulmonary baroreceptor unloading by lower body negative pressure (LBNP) at -15 mmHg. The effector limb was tested by measuring the PNE, FVR, and mean arterial pressure (MAP) response to the cold pressor test (CPT). The postganglionic neuroeffector junction was tested by measuring the venoconstrictive response to local norepinephrine infusion. ECFV was varied by altering dietary sodium. In IDDM subjects on a 250 mmol sodium diet, PNE and FVR responses to LBNP (delta PNE = 0.15 +/- 0.05; delta FVR = 4.3 +/- 1.2) were attenuated compared with controls (delta PNE = 0.36 +/- 0.23; delta FVR = 11.56 +/- 2.72). MAP and FVR responses to the CPT were intact (delta MAP = 9.74 +/- 1.9; delta FVR = 7.02 +/- 3.11) compared with controls (delta MAP = 10.74 +/- 2.69; delta FVR = 8.26 +/- 2.94), but the PNE response was attenuated. The peripheral vasculature was hyperresponsive to norepinephrine infusion in IDDM subjects [mean effective dose (ED50) = 57 +/- 10 ng/min] compared with controls (ED50 = 133 +/- 30 ng/min). Sodium restriction (20 mmol/day) normalized the FVR response to LBNP and the venous response to norepinephrine infusion. The PNE response both to LBNP and the CPT remained attenuated.(ABSTRACT TRUNCATED AT 250 WORDS)