The interaction of TNF- with TNF receptor 1 (TNFR1) activates several signal transduction pathways that leads to apoptosis or NF-B-dependent inflammation and immunity. We hypothesized that host TNFR1 expression contributes to non-infectious lung injury and inflammation commonly observed after bone marrow transplantation (BMT), termed idiopathic pneumonia syndrome (IPS). C57BL/6 TNFR1-sufficient (TNFR1+/+) and TNFR1-deficient (TNFR1-/-) mice were total body irradiated (TBI) with or without cyclophosphamide (Cy) conditioning and given bone marrow plus IPS-inducing donor spleen T cells from B10.BR wild type mice. TNFR1-/- recipient mice exhibited improved early post-BMT survival associated with decreased permeability edema. In addition, the low lung compliance measured in anesthetized-ventilated TNFR1+/+ mice on day 7 after BMT was restored to baseline during TNFR1 deficiency. Importantly, BALF inflammatory cells from TNFR1-/- vs. TNFR1+/+ mice generated less nitric oxide (^.NO) and nitrating species, and exhibited suppressed programmed cell death assessed using flow cytometry. However, cellular infiltration and levels of proinflammatory cytokines and chemokines were generally higher in bronchoalveolar lavage fluids (BALF) collected on day 7 after BMT from TNFR1-/- compared to TNFR1+/+ recipient mice. Results support a major role of host TNFR1 in regulation of ^.NO production and lung dysfunction after allogeneic BMT.