Using northern blot analysis and immunohistochemistry, we assessed the expression and distribution of human epidermal growth factor receptor-1 (HER-1), HER-2, and HER-3 in pancreatic tissues obtained from patients with acute pancreatitis (AP). Overall, HER-1, HER-2, and HER-3 mRNA levels were similar in the normal pancreas and in the pancreas of AP patients. However, three patients exhibited a significant increase in HER-1 mRNA levels. Furthermore, the distribution of the receptors differed with respect to the various cell types in the human pancreas. In the normal pancreas, moderate HER-1 and strong HER-3 immunoreactivity was present predominantly in the cytoplasm of acinar cells and to a lesser extent in the ductal cells, whereas strong HER-2 immunoreactivity was present in the islet cells. In the AP tissues, there was a marked increase in HER-1 immunoreactivity in acinar and ductal-like cells, whereas HER-3 immunoreactivity was less prominent in acini and increased in ductal-like cells. HER-2 immunoreactivity was again mainly evident in islet cells, but was also present in the ductal-like cells. These findings indicate that there is altered distribution of HERs in the pancreas following AP and raise the possibility that HERs may be involved in the process of pancreatic regeneration during recovery from AP.