Vasoplegia resulting from severe burns may persist despite adequate fluid resuscitation and treatment with norepinephrine (NE), vasopressin (VP), and steroids. The adenylate cyclase inhibitor methylene blue (MB), currently used in the burn patient to treat methemoglobinemia, has been used to treat vasoplegia after cardiopulmonary bypass. We report the case of MB infusion in two burn patients refractory to NE. The patients had severe burns, 95 and 80% TBSA not responding to conventional treatment. Fluid requirements were estimated according to Parkland formula and then to maintain a urinary output of 30-50 ml/hr. Patient #1, 95% TBSA, was adrenally insufficient and was receiving steroids according to the Annane protocol, as well as VP at 0.2 U/min. His NE requirements were 55 mcg/kg/min. Patient #2, 80% TBSA, was receiving 20 mcg/kg/min of NE. Circulatory failure was defined as inability to maintain mean arterial pressure >70 mm Hg. Hemodynamic and physiologic parameters were measured before and after infusion of a single dose of 2 mg/kg of MB. Both patients showed dramatic improvements in their shock after MB. Patient #1 had an initial reaction within 30 minutes and reached peak effect at 1 hour. His NE requirements decreased to 0.2 mcg/kg/min and VP decreased to 0.04 U/min. Patient #2 showed effects within 15 minutes of the infusion and by 2 hours the NE was stopped. No adverse side effects were noted in either of the two patients. The fact that MB successfully reversed refractory vasoplegia after severe burns suggests a new tool for treating a small subgroup of patients who exhibit persistent vasoplegia from their burn injury. A controlled randomized trial is needed to test its effects on a large number of patients and graft survival.