BACKGROUND AND OBJECTIVES Alteration of the p53 gene product occurs frequently during progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. METHODS A total of 22 patients with primary colorectal cancer who underwent surgical treatment were examined for chemosensitivity with iable tumor samples using the Histoculture Drug Response Assay (HDRA). Serum samples of these patients for p53 antibodies were obtained before tumor resection and assayed in duplicate using an enzyme-linked immunosorbent assay kit. RESULTS The inhibition index of 5-fluorouracil and cis-diamminedichloroplatinum (CDDP), determined by the HDRA method, in the seropositive group was significantly lower than that in the seronegative group (P < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-fluorouracil and CDDP were revealed depending on the presence of serum p53 antibodies. CONCLUSIONS Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simpler method which correlates with chemosensitivity and may contribute to the selection of favorable chemotherapeutic strategies for colorectal cancer.