Background and aims: Among various causes, nerve alterations and neuroimmune interactions have been suggested to participate in the generation of pain in chronic poncreatitis (CP). In this study, we compared neural changes and the pattern of perineural inflammatory cell infiltrates in three different aetiological forms of CP (alcoholic, idiopathic, and tropical) and evaluated whether differences exist between these groups. Patients and methods: A total of 35 patients with CP (12 tropical, 12 idiopathic, and 11 alcoholic) were included. Ten normal pancreatic tissues obtained from healthy organ donors served as controls. In all samples, the number of nerves, area of neural tissue, nerve size, and percentage of neural tissue and perineural inflammatory cell infiltrates were analysed histologically. Results: The median number of nerves per 10 mm(2) tissue area was 2.3, 4.3, 4.4, and 2.6 in the normal pancreas, alcoholic CP, idiopathic CP, and tropical CP, respectively. Median area of neural tissue per 10 mm(2) was 2550, 21 803, 18 595, and 24 666 mum(2) in the normal pancreas, alcoholic CP, idiopathic CP, and tropical CP, respectively. Median nerve diameter was 36.85 mum in the normal pancreas, 80.6 mum in alcoholic CP, 68.95 mum in idiopathic CP, and 93.05 mum in tropical CP. In comparison with normal controls, all of these parameters were significantly increased except the number of nerves in tropical CP. For all parameters there were no significant differences between alcoholic, idiopathic, and tropical CP. When the degree of perineural inflammation was evaluated, no differences were observed among the three CP groups. Conclusions: Independent of the underlying aetiology, CP is associated with an increase in neural tissue, and neural alterations occur in a similar fashion irrespective of the type of initiating event.