We describe the third case and first successful treatment of hyperacute rejection in a pulmonary allograft recipient and detail the immediate clinical findings. The patient underwent single right lung transplantation for severe emphysema and chronic obstructive pulmonary disease. Three hours after completion of the vascular anatomoses oxygen desaturation and increased airway pressure was noted in combination with graft edema, frothy, pink fluid draining from the bronchial orifice, hemodynamic instability, thrombocytopenia, and coagulopathy. The retrospective cross-match result was reported to be positive. The clinical diagnosis of hyperacute rejection was made. A donor-specific IgG HLA antibody to A2 was identified. The standard immune suppression regimen was immediately modified and a hyperacute rejection protocol applied including plasmapheresis and antithymocyte globulin treatment as well as cyclophosphamide to decrease antibody existence and production. A remarkable clinical recovery was observed after the fifth postoperative day and completion of plasmapheresis when a repeated retrospective cross-match showed significantly decreasing anti-donor reactivity.