Obliterative bronchiolitis has been the major complication in long-term survivors of human heart-lung transplantation at our institution. We have assessed the effect of the introduction of a third immunosuppressive agent, azathioprine, on the rate of decline in airflow variables in eight heart-lung transplant recipients with obliterative bronchiolitis, and have compared this rate with that in five patients who did not receive augmented immunosuppressive therapy. Specifically, the rate of decline in forced expiratory flow rate between 25% and 75% of vital capacity improved considerably after institution of this therapy (-5.25 +/- 2.85 compared with -0.27 +/- 0.66 [mean +/- SD]; p less than 0.005), whereas the effect on the ratio of forced expiratory volume in one second to forced vital capacity was more modest (-3.61 +/- 1.52 compared with -0.54 +/- 0.93; p less than 0.005). The rate of decline in airflow variables was similar in both groups before the institution of therapy with azathioprine. These results show that augmented immunosuppressive therapy is capable of slowing the rate of progression of obliterative bronchiolitis in this population; they also suggest that the obliterative bronchiolitis may represent a form of chronic pulmonary allograft rejection.