We determined risk factors present in patients with Hodgkin disease that predicted the development of diffuse alveolar hemorrhage syndrome (DAH) during autologous bone marrow transplantation (BMT). One hundred twenty-three patients with Hodgkin disease prospectively underwent bronchoscopy with bronchoalveolar lavage (BAL) before receiving BMT. The bronchitis index (BI) of the airways and bronchial and alveolar cell counts and differentials were determined in all patients and compared with 20 normal nonsmoking volunteers. Logistic regression analysis was used to determine factors that predicted for the development of DAH. Visual evidence of bronchial injury was observed regardless of smoking history (BI = 7.8 +/- 0.5 for BMT versus 2.3 +/- 0.5 for volunteers, p = 0.001). BMT patients who developed DAH (n = 14) had significantly greater numbers of bronchial neutrophils and eosinophils compared with DAH-negative (n = 109) patients (bronchial polymorphonuclear leukocytes (PMN), 33 +/- 7% versus 14 +/- 2%, p = 0.006; bronchial eosinophils, 0.9 +/- 0.3% versus 0.4% +/- 0.07%, p = 0.02). Logistic regression analysis revealed that the presence of bronchial PMN > 20% or bronchial eosinophils > zero% were predictive of DAH (p = 0.005 and 0.05, respectively). When both predictors were positive, the rate of DAH was 10 times greater than when both predictors were negative (43% versus 4% DAH occurrence). Survival was also significantly reduced when these predictors were positive. This study demonstrates that bronchial inflammation is present with or without intraluminal inflammatory cells in the majority of patients with Hodgkin disease before BMT. The subgroup of these patients with increased bronchial inflammatory cells are at greatly increased risk for development of DAH and death.