Lung transplantation is now accepted as a viable therapeutic option for patients with end-stage lung diseases, but long-term survival is threatened by bronchiolitis obliterans (BO), which is regarded as a manifestation of chronic allograft rejection. We have used studies of ventilation distribution for the early detection of this complication. In a prospective study of 57 bilateral-lung transplant recipients, we showed that the slope of phase III of the helium single-breath washout, which targets inhomogeneities of ventilation distribution in the terminal and respiratory bronchioles, was particularly sensitive to the development of BO. In a preliminary study using nitrogen multiple-breath washouts, we showed that S(acin) and S(cond), which reflect structural changes in the acinar and conductive lung zones, were both markedly increased in patients with BO. Taken together, these studies demonstrate that monitoring the function of the allograft by measuring the distribution of ventilation in the lung periphery may be a clinically valuable tool.