Very late activation (VLA) receptors mediate cell adhesion to extracellular matrix, mainly by acting as adhesion receptors to fibronectin, collagen, and laminin as well as to other cells. These interactions not only regulate normal cell-extracellular matrix contact, but also are thought to be involved in metastasis and invasive tumor growth. Using immunohistochemistry [the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique] we compared the expression and distribution of VLA receptors in normal pancreatic tissue, chronic pancreatitis, and ductal pancreatic adenocarcinoma. Immunohistochemically, VLA α2 and VLA α6 were moderately to strongly expressed on the basal surface of ductal and acinar cells in normal pancreatic tissue, whereas centroacinar cells predominantly expressed VLA α3 and VLA as. Similarly, pancreatic carcinoma showed an intensive staining for VLA α2 and VLA α6 with a diffuse distribution on the cell surface. Expression of VLA α3 and VLA α5 in pancreatic carcinoma was heterogeneous, ranging from moderate to weak and lost in about 50% of the cells. As our results suggest, cell-basement membrane interaction in ductal and acinar pancreatic cells is primarily mediated through VLA α2 and VLA α6, whereas VLA α3 and VLA α5 are the major VLA receptors on centroacinar cells. In pancreatic carcinoma a loss (VLA as) or redistribution (VLA α2, VLA α6) of VLAs was observed. This redistribution of VLA α2 and VLA α6 may reflect a loss of spatial arrangement of tumor cells and their ability to randomly interact with extracellular matrix structures during invasion and metastasis.