Diffusion MRI of hyperpolarized (3)He shows that the apparent diffusion coefficient (ADC) of (3)He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about (3)He gas diffusivity in explanted human lungs, and describe the relationship between (3)He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (L(m)) measurements--the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via (3)He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and L(m)). An important result is that restricted (3)He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes.