Thirty-two recipients of single, double, or heart-lung transplantation followed-up for at least 3 months posttransplant were retrospectively reviewed to assess the frequency, predictors, and risk factors associated with the development of bronchiolitis obliterans (BO). A clinical definition for the diagnosis of BO was made using the following criteria: persistent and progressive decline in FEF25-75, associated with normal results of cytologic and microbiologic studies for significant pathogens in bronchoalveolar lavage fluid, with a normal chest radiograph. This was correlated with histologic diagnosis and patient outcome. Sixteen (50%) of the patients developed BO, and this was associated with a 56% mortality. All but 1 patient with histologic BO had a clinical diagnosis of BO made (often months) prior to diagnostic biopsy. No patients with normal histologic findings had a clinical diagnosis of BO. More than 3 episodes of histologically documented acute rejections in any 12-month period were eventually associated with a 100% incidence of BO. Cytomegalovirus occurred with greater frequency in patients with BO, and in most cases, preceded or occurred concomitantly with the diagnosis of acute rejection or BO.