Data from 932 patients with leukemia who received bone marrow transplants were analyzed to determine factors associated with an increased risk of developing interstitial pneumonitis. Interstitial pneumonitis developed in 268 patients for a 2-year actuarial incidence of 35 +/- 4% (SD) and with a mortality rate of 24%. Six factors were associated with an increased risk: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.3; p less than 0.0002); older age (relative risk, 2.1; p less than 0.0001); presence of severe graft-versus-host disease (relative risk, 1.9; p less than 0.003); long interval from diagnosis to transplantation (relative risk, 1.6; p less than 0.002); performance ratings before transplantation of less than 100% (relative risk, 2.1; p less than 0.0001); and high dose-rates of irradiation in patients given methotrexate after transplantation (relative risk, 3.2; p less than 0.03). The risk of developing interstitial pneumonitis ranged from 8% in patients with none of these adverse risk factors to 94% in patients with all six. These findings may help to identify patients at high risk for this complication.