We prospectively studied the distribution of ventilation in 22 heart-lung transplant (HLT) recipients. At entry into study, the patients had undergone surgery an average of 6.7 mo earlier, and were followed for a mean period of 16 mo. Vital-capacity (VC) single-breath washouts as well as single-breath washouts using a 1-L inspiration from FRC were performed on a total of 395 occasions. The inhaled gas mixture consisted of 5% He, 5% SF6, and 90% O2, and the expired N2, He, and SF6 concentrations were analyzed. Six patients showed normal standard pulmonary-function tests and indexes of ventilation distribution throughout the study. Five patients gradually developed an irreversible airflow obstruction, presumably due to obliterative bronchiolitis (OB). They showed increases in the slopes of the N2, SF6, and He alveolar plateaus (SN2, SSF6, S(He)), but because S(He) increased more than SSF6, the slope difference (SSF6-S(He)) invariably decreased and became negative in four of five patients. Thirteen patients developed 16 episodes of reversible airflow obstruction as a result of acute infection or rejection of the lung allograft. The alterations in ventilation distribution were qualitatively similar to those seen in patients with OB. We conclude that: (1) ventilation distribution in the lung periphery is normal in HLT recipients with adequate allograft function; (2) the airflow obstruction elicited by OB and acute episodes of lung infection or rejection is accompanied by increases in SN2, SSF6, and S(He) and decreases in SSF6-(He)).(ABSTRACT TRUNCATED AT 250 WORDS)