The eventual recurrence of PAH in this patient is important to note. The “multiple-hit hypothesis” of PAH assumes that a genetic predisposition, combined with environmental factors, leads to the development of idiopathic PAH. Severe pulmonary hypertension developed in our patient, followed by significant improvement in PAH symptoms and hemodynamics following transplant, followed by recurrence of severe PAH following removal of the transplanted lung. While the use of immunosuppressive medication to prevent allograft rejection may have played a role in the patient’s improved PAH, we believe it unlikely, as these medications have not been effective in the treatment of PAH. Rather, with insertion of the allograft in 1994, an enormous shift in the pulmonary circulation (97% of perfusion to the allograft by ventilation-perfusion scan) permitted a great reduction in the endothelial stress to the vascular bed of the native lung. Following years of reduced endothelial stress after receiving the transplant, the patient’s PAH improved significantly. However, as her allograft eventually failed and was then removed, her native load took on a progressively greater proportion of the pulmonary blood flow. This increase in volume and endothelial stress likely permitted recurrent injury to the vascular endothelium, which, combined with a genetic predisposition, led to the return of severe PAH.