The results of the present study of the p53 antioncogene in a broad panel of human cell lines (n = 32) and biopsy specimens (n = 435) from both normal and tumour tissues can be summarized as follows: 1. Cells in primary cultures from normal tissues express very low levels of the p53 protein while strong nuclear accumulation of p53 can be seen in all SV 40 transformed human cell lines and the vast majority of tumour--derived cell lines studied. 2. Similarly, in human tissues strong nuclear p53 expression is found in high proportion of malignancies of various histogenesis, in contrast to benign lesions, nonmalignant tissues surrounding malignant tumours and normal tissues in which the p53 protein levels remain below the limits detectable by common immunohistochemical methods. 3. Sequence analysis of p53 mRNA amplified by polymerase chain reaction (PCR) revealed point mutations in the central region of the p53 gene in several cancer cell lines. Furthermore, very good correlation was found between the presence of such mutations and accumulation of the mutated p53 protein. This study confirms and extends our current view of p53 as the gene most frequently altered in human cancer and suggests that simple immunohistochemical methods can be used to screen for aberrations of this antioncogene.