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Human monoclonal antibody (HuMAb) SK1, a human monoclonal IgM, has previously been shown to react selectively with a wide range of human carcinomas. In this study, the complement-dependent cytotoxicity (CDC) mediated by the HuMAb SK1 was investigated.The presence of AgSK1 on the two studied cell lines, HT29 and PANC-1, was evaluated by the immunocytochemical staining. The intracellular and surface locations of the targeting antigen of HuMAb SK1 were further characterized by the study of flow cytometry. The specific lysis of target cells by the HuMAb SK1 in the CDC assay was studied.In the presence of human complement, the HuMAb SK1 was shown to be effective in the lysis of cultured human gastrointestinal cancer cells as well as the fresh colon cancer cells derived from the patient's specimens. In addition, our data suggested that HuMAb SK1 activated the mouse complement in a similar magnitude.We concluded that HuMAb SK1 showed some promise for future clinical trials. Thein vitroCDC effect of HuMAb SK1 with mouse complement suggested that the antitumor effect of HuMAb SK1 might be successfully studied in the nude mouse model bearing xenografts of human colon cancer as a part of the preclinical evaluation.