The molecular alterations that contribute to the histomorphological changes in chronic pancreatitis are completely unknown. The purpose of our studies in the past several years was to investigate the importance of growth factors and growth factor receptors in chronic pancreatitis. Using immunohistochemistry, Northern blot analysis and in situ hybridization we found a marked overexpression of the epidermal growth factor (EGF) receptor and c-erbB-3. In addition, the pancreas of patients with chronic pancreatitis and pancreatic head enlargement overexpressed c-erbB-2. Polypeptide growth factors such as EGF and transforming growth factor alpha that bind to the EGF receptor were also overexpressed in many chronic pancreatitis samples. Furthermore, enhanced mRNA levels encoding acidic fibroblast growth factor and basic fibroblast growth factor were detectable. These findings indicate a role for growth factors and growth factor receptors in the pathophysiology of chronic pancreatitis and suggest that these factors might contribute to the morphological alterations that occur in chronic pancreatitis in humans.