Background.The aim of our study was to describe the incidence, clinical course, and risk factors for the idiopathic pneumonia syndrome (IPS), compared with those previously described for “idiopathic pneumonia,” after bone marrow transplantation (BMT).Methods.Our study design was a case-series review with determination of risk by comparison with unaffected controls by log-rank or Fisher's exact (two-tailed) test and logistic regression analyses. The study group comprised 1165 consecutive marrow recipients at a single center from 1988 to 1991.Results.IPS was documented in 85 BMT recipients (7.3%) by bronchoalveolar lavage (n=68), open lung biopsy (n=3), or autopsy (n=14). The calculated actuarial incidence for IPS within 120 days after BMT was 7.7%. Median time to onset was 21 days (mean 34±30). Hospital mortality was 74%, and 53 BMT recipients (62%) died with progressive respiratory failure. IPS resolved in 22 patients (26%); 18 patients (21%) survived to discharge. Mechanical ventilation was required by 59 BMT recipients (69%), within a median of 2 days of onset of infiltrates. Two of these 59 recipients (3%) survived to discharge. Pulmonary infection (predominantly fungal) was noted in 7 of 25 (28%) BMT recipients who had an autopsy. Potential risk factors for IPS were assessed in univariate and multivariate logistic regression analyses. Although the incidence was not significantly different between autologous (5.7%) and allogeneic marrow recipients (7.6%), risks were identified only for the latter: malignancy other than leukemia (odds ratio=6.5 compared with aplastic anemia), and grade 4 graft-versus-host disease (odds ratio=5.4 compared with lower grades). No factors were associated with recovery.Conclusions.The incidence of idiopathic lung injury seems lower, the onset earlier, and the risk factors different from those previously reported. The major risks seem to be regimen-related toxicity and multiorgan dysfunction associated with alloreactive processes.