A 32-year-old man with a history of acute myelogenous leukemia (AML) secondary to myelodysplastic syndrome underwent double umbilical cord allogeneic SCT after fludarabine (Flu), cyclophosphamide (Cy), thiotepa, and total body irradiation (TBI) conditioning 6 months after his AML diagnosis. A few weeks after his SCT, he developed severe gastroparesis requiring the placement of a feeding tube. Following this event, his tacrolimus and prednisone doses were increased due to suspicion of graft versus host disease (GVHD) of the gastrointestinal tract. Random mucosal biopsies after an upper and lower gastrointestinal endoscopy were negative for GVHD and the patient continued to require a feeding tube for nutrition. Approximately 14 months after his transplant and while tapering of immunosuppressive agents, he developed severe symptomatic orthostatic hypotension requiring hospitalization for intravenous (IV) fluids. Adrenal insufficiency was thought unlikely due to an appropriately elevated cortisol level and a lack of response to stress dose steroids. An autonomic reflex screen demonstrated severe autonomic dysfunction. Patient underwent a tilt test for 1.5 minutes, following which there was severe progressive blood pressure drop with symptom of dizziness, weakness, and inadequate heart rate response. Beat-to-beat blood pressure responses to Valsalva maneuver showed absent late phase II and phase IV overshoot and prolonged blood pressure recovery time. The quantitative axon reflex sweat test responses were reduced at all sites except forearm. Severe orthostatic symptoms persisted despite maximal doses of midodrine and fludrocortisone and cerebrospinal fluid (CSF) analysis showed elevated protein of 109 mg/dl with normal cell count, glucose, and cytology. Serum autoimmune dysautonomia evaluation which consisted of antibodies to anti-neuronal nuclear antibodies (ANNA-1), striated muscle, acetylcholine receptor (AChR muscle binding and neuronal ganglionic), neuronal K+ channel, GAD-65, and N and P/Q type calcium channel, and ganglioside was negative. Serum and urine protein electrophoresis, HIV testing, and antinuclear antibodies were also negative. Since the development of his AD coincided with tapering of his immunosuppression, an autoimmune etiology was thought as the most likely underlying mechanism. A 5-day treatment course with intravenous immunoglobulin (IVIG) at a dose of 0.4 gm/kg daily resulted in significant improvement in orthostasis and gastroparesis. Posttreatment autonomic reflex screen was not performed due to significant clinical improvement. Soon thereafter, he was able to tolerate oral intake and his functional status significantly improved. A diagnosis of seronegative autoimmune autonomic ganglionopathy was made and he was discharged with maintenance twice weekly IVIG treatments. Orthostasis symptoms recurred following nonadherence, and resumption of IVIG led to rapid clinical improvement. At the time of last follow-up, the response has been sustained for four months.