The aim of this study was to assess the feasibility of using serial bronchoalveolar lavage fluids (BALFs) to characterize the course of cell damage and inflammation in the airways of pediatric patients with acute burn or inhalation injury. This was a prospective, longitudinal, descriptive pilot study conducted at the Burn and Pediatric Intensive Care Units in a tertiary care medical center. Six consecutively intubated and mechanically ventilated pediatric patients with acute inhalational injuries were studied. Serial BALF specimens from clinically indicated bronchoscopies were used to measure DNA and cytokine levels. BALF DNA levels for the six pediatric burn subjects were the highest within the first 72 hours after burn injury and declined thereafter. At the early stages after injury, BALF DNA levels (median [min, max] 3789 [1170, 11,917] ng/ml) were similar to those in adult burn patients and pediatric cystic fibrosis or bronchiectasis patients and was higher than those in pediatric recurrent pneumonia patients. BALF DNA levels in children and adults with inhalation injury correlated significantly with BALF interleukin-6, interleukin-8, and transforming growth factor-β1 levels. The patient with the most severe early visible airway mucosal damage and soot pattern at bronchoscopy, as well as the most extensive burns, also had the highest average early BALF DNA level (11,917ng/ml) and the longest ventilator course and hospital stay. Procedures were well tolerated. In children with acute burn and inhalational injury, airway cellular damage and inflammation (reflected in high BALF DNA levels) appear to peak during the first 72 hours after burn or inhalation injury followed by a slow decline. Serial analysis of factors in airway secretions is feasible and has the potential to reveal important pathophyisiologic pathways and therapeutic targets for the treatment of acute inhalational injuries.