Phospholipase C (PLC) isozymes are believed to play a role in regulating pancreatic exocrine and endocrine secretion. In an attempt to investigate the role of PLC, we examined the distribution patterns of PLC isozymes in the normal rat pancreas by Western blot analysis and immunohistochemistry. Western blot analysis was performed on pancreatic acinar tissues and the islet of Langerhans, which were separated from each other. PLC-&bgr; isozymes (&bgr;1, &bgr;2, &bgr;3, and &bgr;4), &dgr;1, and &dgr;2 were detected in both acinar and islet cells, whereas PLC-&ggr;1 and &ggr;2 were observed only in acinar tissues. On immunohistochemistry, the immunoreactivities of PLC isozymes except for PLC-&ggr;1 were observed as follows: PLC-&bgr;1, in both the exocrine and endocrine tissues; PLC-&bgr;2, mainly in the periphery of the islet and acinar cells; PLC-&bgr;3, in the periphery of the islet and in some ductal epithelium; PLC-&bgr;4, through the islet of Langerhans and ductal epithelium; PLC-&ggr;1, not detected in pancreatic tissue; PLC-&ggr;2, mainly in acinar cells; PLC-&dgr;1 and &dgr;2, in the islet and in ductal epithelium. These results suggest that the intrapancreatic site-specific existence of PLC isozymes may modulate pancreatic exocrine and endocrine functions through a PLC-mediated signal transduction.