p53 aberrations are frequent in colorectal carcinogenesis (40-70%). Because p53 gene mutations typically result in increased p53 protein concentration in tumor cells, this cellular protein might become immunogenic during tumor development. To test this hypothesis, serum p53 antibodies were quantitatively analyzed in 229 patients with colorectal cancer, using an immunofluorometric procedure. Circulating antibodies against p53 were found in 23% (53/229) of the patients. We quantified antibody concentrations in all positive sera and found that they varied from 300 to 500,000 arbitrary units/1. Sequential analysis of positive sera from 3 patients showed that p53 antibody concentrations change during the course of the disease, reflecting progression or regression. No association was found between the presence of p53 antibodies and age, sex, stage, histological grade and patient relapse-free or overall survival. These data demonstrate that antibody generation against the p53 tumor-suppressor protein is a relatively common event in colorectal cancer and that serological analysis for p53 antibodies may have some value for patient monitoring. The test has no value for prognosis.