Deposition of nanosized particles in the pulmonary region has the potential of crossing the blood-gas barrier. Experimental in vivo studies have used micron-sized particles, and therefore nanoparticle deposition in the pulmonary region is not well understood. Furthermore, little attention has been paid to the emphysematous lungs, which have characteristics quite different from the healthy lung. Healthy and emphysematous replica acinus models were created from healthy and diseased human lung casts using three-dimensional reconstruction. Particle concentration and deposition were determined by solving the convective-diffusion equation numerically for steady and unsteady cases. Results showed decreased deposition efficiencies for emphysema compared to healthy lungs, consistent with the literature and attributed to significant airway remodeling in the diseased lung. Particle diffusion was found to be six times slower in emphysema compared to healthy model. The unsteady state simulation predicted deposition efficiencies of 96% in the healthy model for the 1 nm and 3 nm particles and 94% and 93% in the emphysema model for the 1 nm and 3 nm particles, respectively. Steady state was achieved in less than one second for both models. Comparisons between steady and unsteady predictions indicate that a steady-state simulation is reasonable for predicting particle transport under similar conditions.