The experiments described in this study examined cell membrane oligosaccharides, malignancy-related cell phenotypes and tumor cell susceptibility to the killing effect of human cytotoxic cells. Short term breast carcinoma (BCa) cell lines were prepared from biopsies obtained from patients at each of the pathological Stages I, II, III and from patients with disseminated liver metastasis. Five patients at each stage donated the tissue. To obtain large enough quantities, the cells were cultured as monolayers for a brief period, then transferred to roller bottles using serum-free hormone defined medium. Natural killer (NK) cells, lymphokine (IL-2)-activated killer (LAK), tumor-infiltrating lymphocytes (TIL) and peripheral cytotoxic lymphocytes (CTL) from patients with BCa at PS I were used as the effector cells. Susceptibility of the tumor cells to the killing effects of the effector cells was monitored by the well established 4 h 51Cr-release assay technique. Growth factor expression, oncogenicity in athymic female mice and colonigenicity in soft agar were used as parameters to monitor breast carcinoma cell malignancy phenotypes. The cell membrane oligosaccharides were determined from the carbohydrate elution profiles from BioGel P-6 columns. The results indicate a correlation between progression of malignancy from PS I to the metastatic stage PS IV, and the magnitude of malignancy phenotypes, resistance to the host killer cells and oligosaccharide profile shift to a higher molecular size with increased sialylation and fucosylation of the carbohydrate moieties.