The objective of the study was to determine whether the CXC chemokine receptor (CXCR) 4 ligands ubiquitin and stromal cell-derived factor (SDF)-1α are detectable in bronchoalveolar lavage fluid (BALF) after burn and inhalation injury and whether their concentrations in BALF are associated with injury severity, physiological variables, or clinical outcomes. BALF was obtained on hospital admission from 51 patients (48 ± 18 years) with burn (TBSA: 23 ± 24%) and inhalation injury (controls: 10 healthy volunteers, 42 ± 8 years). BALF was analyzed for total protein and for ubiquitin and SDF-1α by enzyme-linked immunosorbent assay. Ubiquitin/SDF-1α levels were normalized to total BALF protein content. The extent of inhalation injury was determined during bronchoscopy using a standardized scoring system. Percent TBSA, Baux scores, revised Baux scores, and clinical variables were documented. Ubiquitin and SDF-1α were detectable in 40% of normal BALF specimens. After injury, ubiquitin was detectable in 90% (P < .01 vs control) and SDF-1α in 10% of the specimens (P < .05 vs control). While SDF-1α levels were reduced in patients (P < .01), ubiquitin levels were increased (P < .01). Ubiquitin concentrations correlated inversely with grade of inhalation injury, revised Baux scores, and resuscitation fluid requirements (Spearman correlation coefficients [r]: -.3, -.33, and -.45, respectively). Ubiquitin levels correlated positively with arterial oxygenation at the time of bronchoscopy (r: .35). BALF levels of CXCR4 agonists are differentially regulated after burn and inhalation injury. Increases in BALF ubiquitin after inhalation injury may maintain CXCR4-mediated lung protection and repair processes. The finding that BALF ubiquitin decreased with higher grades of inhalation injury may provide a biological correlate for an insufficient local inflammatory response after severe inhalation injury.