We studied the combination effect of cisplatin(CDDP) plus etoposide(VP-16) in an established gastric cancer cell line, KATO-III, and also highly purified fresh human tumor cells obtained from 55 gastric cancer patients, using MTT assay. The synergistic effects of CDDP plus VP-16 were shown by both the fractional product method and median effect plot analysis in KATO-III cells, and by fractional product method in fresh human gastric cancer cells. The combination with CDDP and VP-16 showed the synergistic antitumor effects in not only KATO-III cells, but also fresh human gastric cancer cells. The antitumor effects of CDDP were enhanced by early exposure of VP-16 in KATO-III cells. The combination effects of CDDP and VP-16 were more potent in poorly differentiated gastric cancer, compared with well-differentiated cell types. Thus, it is suggested that the combination of CDDP plus VP-16 is useful in the anticancer chemotherapy of gastric cancer patients.