The immunohistochemical localization of cathepsins D and E in 44 cases of human gastric carcinoma, using antibodies specific for each enzyme, were investigated. Cathepsin D- and E- positive carcinoma cells were present in all samples. However, the staining intensity varied from cell to cell in the same carcinoma tissue as well as among samples. The most intense immunostaining of both cathepsins was often found in the cells, which were present at the advancing margin of the carcinoma tissues. The incidence of this peculiar localization of intensely stained carcinoma cells significantly correlated with the progression of the carcinoma tissue (D, P < .05; E, P < .01) and with occurrence of the lymph node metastasis (D and E, P < .05). There was no statistical significance between this localization and the histological type (differentiation) of the carcinoma tissues. Cathepsin-positive inflammatory cells infiltrated in and around the carcinoma tissue, and intensely stained inflammatory cells were often located in the stroma at the border of the carcinoma tissue. However, no statistical correlation was noted between the localization of cathepsin-positive inflammatory cells at the border and the stage of progression or the incidence of metastasis. These results indicated that cathepsins D and E in the carcinoma cells located at the advancing margin play an important role in the invasion and subsequent metastasis of human gastric carcinoma. Meanwhile, cathepsin-positive inflammatory cells seem to be less responsible for the biological behavior of carcinoma cells than those in the carcinoma cells themselves.