Objective: To develop a feasible model of early chronic lung disease (CLD) in mechanically ventilated newborn piglets. Rationale: Published models of CLD in ventilated animals are very time-consuming and expensive. There is an obvious need for a reproducible, valid and affordable non-primate animal model of CLD. Methods: Sedated and paralyzed newborn piglets from different litters (n=12) received standardized lung lavage with normal saline followed by 4 hours of identical ventilation at a high peak inspiratory pressure (PIP = 40 cm H2O) to create acute lung injury. Subsequently, all animals were mechanically ventilated for further 24 hours during which PIP and FiO2 were regularly adjusted to maintain normal arterial blood gases. Lung histology was reviewed by a single and independent pathologist using a previously described scoring system (Tsuno et al: Am Rev Respir Dis 1991: 143; 1115). Results: The mean a/A oxygen tension ratio at the end of the experiment was 0.35 (SD 0.22); mean ventilator efficiency index was 0.25 (SD 0.14). All animals had hyaline membrane formation (3 mild, 3 moderate, 6 severe). Eight of 12 piglets had histologic evidence of interstitial fibrosis (4 slight or mild, 4 moderate). Organization of alveolar exudate was seen in 10/12 animals (4 slight or mild, 5 moderate, 1 severe). Conclusion: This neonatal piglet model of early CLD after acute lung injury is reproducible across litters and requires < 36 hours of experimental time. Speculation: The availability of such a feasible animal model may prove useful in the evaluation of strategies to improve lung repair after acute injury. (Supported by MRC Canada).