Clinical use of staple lung volume reduction surgery (LVRS) has proliferated for treatment of emphysema despite limited data regarding efficacy or optimal techniques. Recent studies in animal models of obstructive lung disease describe the decrease in lung compliance and increase in airway support as mechanisms of an improvement in pulmonary functions analogous to human data. We describe contrasting results in an animal model of bullous lung disease with a mixed but predominantly restrictive pattern of lung disease. Mixed restrictive and bullous lung disease was induced in 17 New Zealand white rabbits with i.v. Sephadex beads and endotracheally instilled carrageenan. Unilateral stapled lung volume reduction surgery was performed at 5 weeks postinduction of emphysema on the right lower lobe by lateral thoracotomy using a pediatric stapler. Static trans-pleural pressures were measured at 60, 40, and 20 cm3 inflation at preinduction (baseline), pre- and postoperatively, and 1 week postoperatively in anesthetized animals. Lungs were then harvested en bloc and examined histopathologically. The effects of volume reduction surgery on static lung compliance, lung conductance, and forced expiratory flows (FEF) were assessed. Five weeks after induction of lung disease, the animals had no significant change in static compliance and forced expiratory volume in 0.5 s (FEV0.5) or lung conductance compared to baseline. Immediately following LVRS, the animals showed a significant decrease in static compliance, FEV0.5, and conductance. One week postoperatively, compliance increased to approximately baseline levels along with a slight increase in FEFs and conductance toward preoperative levels. Histology examination revealed restrictive and bullous lung disease. Thus, we have demonstrated the feasibility of using an animal model for evaluation of volume reduction therapy for restrictive-obstructive lung disease. Physiologically, this model showed decrease conductance and decreased forced expiratory flows following lung volume reduction despite increased recoil. This is in contrast to increased conductance and flows seen in humans with severe emphysema following surgery and suggests that current criteria excluding patients with a significant restrictive component to their lung disease from LVRS surgery may be justified.