The alveolar air-tissue interface affects the lung NMR signal, because it results in a susceptibility-induced magnetic field inhomogeneity. The air-tissue interface effect can be detected and quantified by measuring the difference signal (Delta) from a pair of NMR images obtained using temporally symmetric and asymmetric spin-echo sequences. The present study describes a multicompartment alveolar model (consisting of a collection of noninteracting spherical water shells) that simulates the behavior of Delta as a function of the level of lung inflation and can be used to predict the NMR response to various types of lung injury. The model was used to predict Delta as a function of the inflation level (with the assumption of sequential alveolar recruitment, partly parallel to distension) and to simulate pulmonary edema by deriving equations that describe Delta for a collection of spherical shells representing combinations of collapsed, flooded, and inflated alveoli. Our theoretical data were compared with those provided by other models and with experimental data obtained from the literature. Our results suggest that NMR Delta measurements can be used to study the mechanisms underlying the lung pressure-volume behavior, to characterize lung injury, and to assess the contributions of alveolar recruitment and distension to the lung volume changes in response to the application of positive airway pressure (e.g., positive end-expiratory pressure).