Obliterative bronchiolitis remains the leading cause of morbidity and mortality in long-term survivors after heart-lung transplantation. Despite enhanced immunosuppressive therapy, a significant number of patients progress to end-stage respiratory failure, leaving retransplantation as the only potential therapeutic option. Between October 1986 and August 1990, 25 heart-lung recipients (mean age 22 +/- 2 years) underwent repeat heart-lung transplantation at an average of 21 months after their first procedure. Twenty-one patients (83%) were ventilator dependent at the time of retransplantation. The Kaplan-Meier survival at 1, 6, 12, and 24 months was 52%, 33%, 25%, and 25%, respectively. Postoperative complications included bleeding, multisystem organ failure, and infection. Obliterative bronchiolitis resulted in death or graft failure in three patients between 12 and 36 months after the second transplantation. Five patients were currently alive at the time this article was written, with a median follow-up of 54 months. Three were in New York Heart Association class I, and two had obliterative bronchiolitis with class III symptoms. Recently, we investigated the role of single lung retransplantation in nine heart-lung recipients (mean age 23 +/- 3 years). The mean interval between procedures was 36 months, and eight patients (88%) were ventilator dependent. The Kaplan-Meier survival at 1, 6, 12, and 24 months was 89%, 67%, 67%, and 50%, respectively. We observed significantly less perioperative morbidity in this group. Five patients were alive (median follow-up 20 months); four were in New York Heart Association class I or II, and one was in New York Heart Association class III with recurrent obliterative bronchiolitis. We did not have enough patients to perform multivariate survival analysis. Survival curve comparisons with the use of the Wilcoxon test did show that the absence of performed antibodies in the recipient (panel reactive antibody frequency less than 10%) was associated with significantly improved survival after retransplantation. We also noted trends for improved survival in patients who had retransplantation at least 18 months after their original transplantation and in patients with negative preoperative sputum cultures. Retransplantation is a high-risk procedure that can result in rehabilitation in otherwise incapacitated patients. Single lung retransplantation appears to be the preferred option in carefully selected patients.