Putative mechanims of regional lung volume changes during the respiratory cycle are discussed controversially, since both, alveolar recruitment and isomorphic alveolar distension, have been recently proposed. Because a better understanding of regional lung mechanics is essential to optimize ventilatory settings in patients, we analyzed alveolar dynamics by intravital microscopy. In anesthetized and ventilated Balb/c mice, a thoracic window was excised and resealed by a transparent membrane, providing visual access to the right lung under closed thorax conditions. Subpleural alveoli were visualized by dark-field illumination and areas (AAlv ), perimeters (PerAlv ) and numbers (nAlv ) of two-dimensional alveolar projections were determined during in- and expiratory plateaus at airway pressures of 0 to 12 cmH2O in 2 cmH2O increments. Mechanical inflation from 0 to 12 cmH2O increased AAlv linearly from 1455±86 mm 2 to 2390±125 mm 2. No alveolar recruitment or derecruitment was observed during the respiratory cycle. At airway pressures of 4 to 10 cmH2O, alveoli distended isomorphically as indicated by a constant ratio of AAlv /PerAlv2 of 0.907±0.002, but became unstable at lower pressures (AAlv /PerAlv2<0.9). These data show that regional lung volume changes in the ventilated mouse lung are attributable to isomorphic and anisomorphic alveolar distension, but not recruitment.