We showed previously that removing 55-58% of the lung by right pneumonectomy (R-PNX) in adult dogs triggers compensatory growth of the remaining lung but removing 42-45% of the lung by left PNX (L-PNX) does not. We also showed that following right PNX, supplemental alltrans retinoic acid (RA) selectively enhances alveolar capillary endothelial cell volume (J. Appl. Physiol. 96:1080-9, 2004). We hypothesized that RA supplementation might enhance compensation following left PNX, and tested this hypothesis by administering RA (2 mg/kg/day, 4 days/week) or placebo orally to litter-matched adult foxhounds for 4 mo following left PNX. Resting lung function was measured under anesthesia. Air and tissue volumes of the remaining lung were assessed by high resolution CT scan ante-mortem and by detailed postmortem morphometric analysis of the fixed lung. There was no significant difference in resting lung function, lung volume, alveolar structure or septal ultrastructure between RA and placebo treatment groups. We conclude that RA supplementation does not induce post-PNX compensatory lung growth in the absence of existing cellular growth activities initiated by other primary signals.