The immunohistochemical localization of group II phospholipase A2 (PLA2) in normal fetal and adult human pancreases, 5 chronic pancreatitis, and 30 pancreatic ductal carcinomas was investigated. Furthermore, pancreatic carcinoma cases were correlated with histologic type, tumor size, vascular involvement, lymphatic involvement, perineural invasion, lymph node metastasis, amount of interstitial tissue in the tumor, growth pattern of the tumor, and clinical stage. In the normal pancreases, almost all of acinar cells and a few cells of small and large ducts were immunoreactive in a supranuclear pattern. In chronic pancreatitis, immunoreactivity was retained in several acini, islet cells, and ductal cells, but the staining was diminished in acinal cells of atrophic lobules. A strong immunoreactivity was found in the cells of hyperplastic ducts. In pancreatic ductal carcinomas, the immunoreactivity was observed in 25 cases (83%). Eighteen of 25 (72%) immunoreactive cases showed a cytoplasmic granular or luminal surface pattern, both of which were not observed in the normal pancreas. Among the clinicopathological parameters of pancreatic cancer, the incidence of expression of this enzyme was significantly higher in infiltrative type cancers than in expansive and localized tumors. Furthermore, the expression of group II PLA2 was significantly higher in the tumor with larger amount of interstitial tissue than in that with smaller amounts of interstitial tissue. These results suggest that expression of group II PLA2 in human pancreatic ductal carcinomas is possibly involved in the proliferation of interstitial tissue directly or indirectly through prostaglandin production.