Experiments were undertaken to investigate a genetic event involved in leukemogenesis in adult T-cell leukemia (ATL). For this purpose, the p53 gene was chosen for study, since alteration of the gene has been found in a wide variety of human cancers. Structures and expression of the p53 gene in ATL cells were investigated by Southern and Northern blot analyses and a polymerase-chain-reaction single-strand conformation-polymorphism (PCR-SSCP) analysis. Either subtle alterations of the p53 gene or the absence of detectable level of p53 mRNA were found in 2 of 3 acute ATL cell lines and 2 of 12 acute ATL fresh samples. In contrast, no mutation was detected in 4 cases with less aggressive types of ATL (3 chronic and 1 smoldering ATL cases). Mutations found in acute ATL cells occurred in regions highly conserved in evolution and all the cells carrying p53 mutation showed loss of the other p53 allele. These results suggests that alteration of the p53 gene may contribute to progression of the disease in some cases of ATL.