Abstract only Deer mice are native to high altitude (HA) at White Mountains in the Eastern Sierra Nevada. A colony has been maintained at a low altitude (LA) at the University of California Riverside (UCR, 252 m) and the Peromyscus Genetic Stock Center (Columbia, SC, 98 m), for 18 generations and shown to remain genetically similar to the wild strain. To examine how these mice re‐acclimatize to HA, one group (5 weeks old) was brought to the Barcroft Laboratory of the University of California White Mountain Research Center (HA, 3,800 m, n=13, body mass (BM) = 18.8±3.3 g) where they resided for 10 weeks before being studied at HA (15 weeks old). An age‐matched group was maintained and studied at UCR (LA, n=13, 22.5±4.1 g). Both groups were compared to outbred laboratory mice (Swiss Webster, SW) of similar age studied at UT Southwestern (80 m, n=8, 36.6±2.1 g). Following measuring maximal O 2 uptake (V O2max ), mice were anesthetized and mechanically ventilated. Lung function was measured by a rebreathing technique via a tracheal cannula. A test gas mixture (0.3% CO, 0.5% Ne, 0.8% C 2 H 2 , in either 40% or 90% O 2 and balance of N 2 ) was delivered to the lung using a calibrated syringe and the mixture rebreathed for a pre‐determined period. Initial and final gas samples were diluted by a known factor and the concentrations measured by a gas chromatograph. Airway pressure‐volume curve was measured at incremental inflation volumes, and capillary blood hematocrit (Hct) was measured. Following euthanasia the lungs were fixed by tracheal instillation of 2.5% glutaraldehyde at 25 cmH 2 O of airway pressure. Lung volume was calculated from Ne dilution. Lung diffusing capaicty (DL CO ) and pulmonary blood flow (Q) were calculated from the exponential disappearance of CO and C 2 H 2 , respectively. Duplicate measurements were obtained at each condition. From measurements made at two alvoelar O 2 tensions (PAO 2 ) and the Hct, DL CO was expressed at a standard PAO 2 (120 mmHg) and Hct (0.45). Results normalized to BM (mean±SD) were compared across groups by ANOVA. P<0.05: * vs. SW, † vs. LA. Compared to SW mice, BM was lower in deer mice (LA 22.5±4.1*, HA 18.8±3.3*† vs. SW 36.6±2.1 g); Hct was also lower (LA 0.42±0.02*, HA 0.44±0.04* vs. SW 0.45±0.04) but BM‐specific lung function results were similar between LA deer mice and SW mice. Compared to LA deer mice, HA deer mice had a lower BM; however, BM‐specific V O2max , Hct, and standardized DL CO were similar. Resting lung volume (HA 66.2±16.9 † vs. LA 47.2±10.0 ml.kg −1 ), and Q (HA 242±150 † vs. LA 142±47 ml.min.kg −1 ) were significantly higher. Postmortem volume of the fixed lung was also higher (HA 41.3±3.7 † vs. LA 33.2±5.6 ml.kg −1 ). Thus, deer mice bred at LA do not develop the expected increase in Hct or the decrement in V O2max upon re‐acclimatization to HA, indicating retention of phenotypic plasticity, which may be attributed to both structural (larger lung volume) and non‐structural (higher Q) mechanisms. It remains to be determined whether the larger lung volume in HA‐reacclimatized deer mice is accompanied by accelerated structural lung growth. Support or Funding Information Support: National Science Foundation Grant 145700