We sought to identify characteristics of pancreatic nerves that were altered in chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed for the number and size of nerves, their association with inflammatory infiltrates, and their fine structure. The mean diameter of nerves in these patients was significantly greater than in controls, whereas the mean area of tissue served per nerve was significantly less than in controls. Foci of inflammatory cells, prominent in some specimens, sometimes were associated with nerves and ganglia, but inflammatory foci and neural elements also existed separately. Invasion of nerve tissue by inflammatory cells was observed but was not massive. Ultrastructural changes were detected in nerves. Individual nerve fibers showed evidence of damage, and there was evidence of edema in the nerve bundle. The perineurial sheath was altered so that it no longer provided a barrier between the surrounding connective tissue and the internal neural components. The results of this study indicate that nerves are preferentially retained while parenchyma degenerates and is replaced by fibrosis during chronic pancreatitis, but that they are retained in an altered condition. Increased mean diameters of nerves in chronic pancreatitis argues against pain being caused by constriction due to fibrosis. It is likely that both sensory and motor nerve fibers are affected by this alteration.