RATIONALE HIV seropositivity has long been considered a contraindication to lung transplantation, primarily because of the potential risks of added immunosuppression. In the past decade, however, experience with kidney and liver transplantation in the setting of HIV infection, with achievement of satisfactory outcomes, has grown considerably. This promising development has created a need to reconsider this contraindication to lung transplantation. OBJECTIVES There is presently limited evidence upon which to base medical decision-making regarding lung transplantation in individuals with HIV infection. In our present study, we wished to extend the existing literature by reporting the outcomes of three individuals with HIV infection who underwent lung transplantation at two centers. METHODS We compiled data for a case series of three HIV-infected subjects undergoing lung transplantation at two centers. MEASUREMENTS AND MAIN RESULTS We reviewed medical records to investigate the effects of lung transplantation on the course of HIV infection, the development of HIV-related opportunistic infections or malignancies, the occurrence of lung transplant and HIV drug interactions, and the extent of acute rejection. Subject 1, who underwent transplantation for HIV-associated pulmonary arterial hypertension, experienced recalcitrant acute rejection requiring a lymphocyte-depleting agent with subsequent rapid development of bronchiolitis obliterans syndrome. Subjects 2 and 3, who underwent transplantation for idiopathic pulmonary fibrosis, experienced mild acute rejection but remain free from chronic rejection at 4 and 2 years after transplant, respectively. CONCLUSIONS Lung transplantation may be feasible for carefully selected patients in the setting of controlled HIV infection. On the basis of our experience with three patients, we caution that acute graft rejection may be more common in such patients.