BACKGROUND: Detection of p53 antibodies in serum might be an effective indirect procedure to detect alterations of the p53 gene. AIMS: To assess the prevalence and the variation under treatment of p53 antibodies in patients with colorectal cancer. PATIENTS AND METHODS: Fifty four patients with colorectal cancer (26 men and 28 women, mean age 65, range 33-90 years) and 24 patients with non-malignant digestive disease were tested for p53 antibodies by enzyme linked immunosorbent assay (ELISA), and for the carcinoembryonic antigen and carbohydrate antigen 19.9. Immunohistochemical detection of p53 protein tumour overexpression was performed in 38 cases. RESULTS: Fourteen patients (26%) with colorectal cancer but none of those with non-malignant disease displayed p53 antibodies. Overexpression of p53 was shown by immunohistochemistry in 22 patients (58%), 10 of whom also had p53 antibodies. The antibodies were present in four patients with high carcinoembryonic antigen and three patients with high carbohydrate antigen 19.9 concentrations, but also in 10 patients (33.3%) with normal values of these markers. The ratio of p53 antibodies decreased in 11 of 13 patients after tumour resection. In two patients variations in p53 ratio strongly correlated with tumour relapse or progression. CONCLUSION: Testing for serum p53 antibodies constitutes a useful technique for assessing alterations in p53 and may help physicians to follow up patients with colorectal cancer.