STUDY OBJECTIVES: The efficacy of antithymocyte induction therapy in lung transplantation is controversial, and its use varies from center to center. We hypothesized that rabbit antithymocyte globulin (RATG) induction therapy would decrease acute rejection after lung transplantation, and we designed a single-center, randomized, prospective study to test this hypothesis. DESIGN: A total of 44 single or bilateral adult lung transplant recipients were randomly assigned to receive either RATG induction therapy (dosage, 1.5 mg/kg/d for 3 days) at the time of transplantation, along with conventional immunosuppression (cyclosporine, azathioprine, and prednisone), or conventional immunosuppression alone with no induction therapy. RESULTS: Although a similar number of biopsies were performed in each group, the number of patients experiencing biopsy-proven grade II or greater acute rejection was significantly reduced in the group receiving RATG induction therapy (23% incidence), as compared to the patients treated with conventional immunosuppression alone (55% incidence; p = 0.03). In addition, there was a nonsignificant reduction in the incidence of bronchiolitis obliterans syndrome at the conclusion of the study in patients who received RATG induction (20%), as compared to patients in the control group (38%). The incidence of posttransplant infections and malignancies were similar between the two groups. CONCLUSION: Induction therapy with RATG significantly reduces the incidence of acute allograft rejection after lung transplantation.