C-erbB-2 is one of the most well known oncogenes in human malignant tumors, and it is expressed in about 8 - 20% of gastric carcinomas. With overexpression of the c-erbB-2, the cancer cells may acquire the ability to resist to host defense mechanism against tumors, but the mechanisms underlying this phenomenon is not known. In order to study the mechanism implicated by this phenomenon, the expressions of the c-erbB-2 protein on human gastric cancer cells were evaluated in relation to their sensitivity to NK cytotoxicity and alterations on their surface molecules(class I-HLA and ICAM-1). First, single cell suspensions were prepared from primary gastric cancer tissue and from malignant cells from ascites fluid due to gastric cancer. Then the expression of c-erbB-2 protein was determined by immunohistochemical staining and compared by flow cytometry. NK cytotoxicity was measured by 51Cr release assays. Surface molecules such as class I-HLA and ICAM-1 of gastric cancer cells were also measured by flow cytometry. c-erbB-2 positive cancer cells were less sensitive to NK cytotoxicity than c-erbB-2 negative cancer cells. Higher expressions of class I-HLA molecules and lower expressions of ICAM-1 molecules were observed in cancer cells that were c-erbB-2 positive and NK resistant. These results suggest that c-erbB-2 positive cancer cells could get their highly malignant potential by changing their sensitivity to NK cytotoxicity and this might be partly due to the altered expressions of surface molecules, such as class I-HLA and ICAM-1, that could be targets recognized by NK cells.