Serum samples taken from children bearing a wide variety of tumors were screened for the presence of circulating antibodies against the cellular tumor antigen p53. There was a significant correlation (p less than 0.001, n = 119) between the presence of such antibodies and the occurrence of cancer; 12% of the sera tested were positive. These sera were derived from children with a wide range of tumor types. In particular, 21% of the sera obtained from children suffering from a B-cell lymphoma contained anti-p53 antibodies. We were not able to establish a correlation between the secretion of p53-reactive antibodies and any other parameters, such as the age or sex of the child, presence of metastasis, stage or prognosis of disease, or treatment regimen. These results therefore show that the development of p53 immunogenicity is associated with a wide range of neoplastic diseases in children, and in particular with the presence of a B-cell lymphoma.