OBJECTIVE To characterize physical and inflammatory injury that may result from repeated intubation, independent of positive-pressure ventilation; and to determine whether corticosteroids can attenuate injury and or inflammation that may result from repeated intubation. METHODS A 4-hr animal protocol. METHODS All work was done in the animal laboratory at the Alfred I. DuPont Hospital for Children. METHODS Neonatal piglets (2-8 days old; 2.5 ± 0.4 kg) were intubated and randomized to four groups (n = 8 each) to be followed over 4 hrs. Groups were control (not reintubated), injured (reintubated every 0.5 hr), intratracheal pretreatment with 1 mg of nebulized budesonide (intratracheal pretreated), or intravenous pretreatment with 0.3 mg/kg of dexamethasone (intravenous pretreated). METHODS Each pig was sedated for the duration of study and had a 3.5F catheter inserted in the femoral artery for blood sampling and blood pressure measurement every hour. After 4 hrs, each pig was killed, and tissue was harvested for histology and interleukin-6 assays. RESULTS Laryngeal tissue interleukin-6 content was greater in the injured group compared with the control group (p < .05). In the intratracheal pretreated group, the interleukin-6 content of laryngeal tissue was greater compared with the control group (p < .05), whereas the intravenous pretreated group was not different from the control group. The reintubation injury resulted in plasma interleukin-6 levels that, compared with control, were greater in the injured and intratracheal pretreated groups (p < .05). Quantitative histology showed that the degree of tracheal injury was higher in injured and intratracheal pretreated groups compared with the control group (p < .05). CONCLUSIONS Repeated intubation alone results in significant tracheal trauma and systemic inflammation. Intravenous but not inhaled steroids attenuated the injury.