The efficacy of a combination of systemic antibiotics and a steroid in the prevention of acquired subglottic stenosis (ASGS) was evaluated employing a previously developed canine animal model. Thirty-five healthy, postweanling mongrel puppies aged 5 weeks were each intubated for 14 days with an uncuffed polyvinyl endotracheal tube. Twenty puppies received intramuscular dexamethasone (1 mg) daily, and procaine penicillin (100,000 IU) and dihydrostreptomycin (0.125 g) in two divided doses on the day of intubation and each day thereafter until the completion of the study. The remaining 15 puppies served as a control group and received no medical therapy. Animals from both groups were killed at 5, 7, 12, 15, 20, 30, and 56 days following intubation. Comparative examinations of the laryngotracheal complexes of treated and control dogs showed that there was no significant difference between the two groups in the ultimate degree of ASGS attained, as determined by intraluminal cross-sectional area analysis, or in the extent of the lesion as documented by gross and microscopic histology. This investigation showed that the specific systemic combination of two antibiotics and a steroid used in the study was not efficacious in the prevention of ASGS in a canine animal model; for this reason we question the benefit of analogous medical regimens employed to prevent ASGS in infants and children who require long-term endotracheal intubation.