The risks for the development of idiopathic pneumonia after allogeneic BMT were assessed in a case-series review at a single marrow transplantation center. All allogeneic marrow recipients (n = 299) (age range 1-60 years) with severe aplastic anemia (SAA) transplanted from family member donors after conditioning with CY were evaluated. Post-grafting immunosuppression consisted of MTX alone in 205 patients (69%), CY alone in 16 (5%) and a combination of the two in 78 (26%). The incidence estimate for any pneumonia within the first 200 days after transplant was 18% (95% confidence interval = 14-24%). Of 48 cases of pneumonia, CMV infection was documented in 44%, 21% were idiopathic and the remainder were either due to other infections or were not evaluated. The effect of acute GVHD on the incidence of pneumonia was examined using multivariate Cox proportional hazards models which included covariates for potential confounding factors. Consistent with previous reports, acute GVHD was associated with an increased incidence of any pneumonia (relative risk (RR) = 3.5, 95% Cl = 1.9-6.9; p < 0.001). Specifically, acute GVHD also was associated with the largest risk of idiopathic pneumonia (RR = 5.0, 95% Cl = 1.1-22; p = 0.04). In conclusion, recognition of acute GVHD as a risk factor for idiopathic pneumonia suggests that mechanisms in addition to chemoradiation damage are responsible for non-infectious lung injury after BMT.