The lungs undergo expansion and contraction during the respiratory cycle. Since many disease or injury conditions are associated with the biomechanical or material property changes that can alter lung function, there is a great interest in measuring regional lung ventilation and regional mechanical changes. We describe a technique that uses multiple respiratory-gated CT images and non-rigid 3D image registration to make local estimates of lung tissue expansion. The degree of regional lung expansion is measured using the Jacobian (a function of local partial derivatives) of the registration displacement .eld. We compare the ventral-dorsal patterns of lung expansion estimated in both retrospectively reconstructed dynamic scans and static breath-hold scans to a xenon CT based measure of speci.c ventilation and a semi-automatic reference standard in four anesthetized sheep studied in the supine orientation. The regional lung expansion estimated by 3D image registration of images acquired at 50% and 75% phase points of the inspiratory portion of the respiratory cycle and 20 cm H2O and 25 cm H2O airway pressures gave the best match between the average Jacobian and the xenon CT speci.c ventilation respectively (linear regression, average r2 = 0.85 and r2 = 0.84). The registration accuracy assessed by 200 semi-automatically matched landmarks in both the dynamic and static scans show landmark error on the order of 2 mm.