The status of the p53 gene in lymphoblastoid cell lines (LCLs) and Burkitt lymphoma cell lines (BLs) was investigated. Southern blot analysis demonstrated that no major deletions or rearrangements had occurred in the p53 gene in any of the cell lines. The p53 protein was examined by immunoprecipitation using two monoclonal anti-p53 antibodies. PAb1801 recognizes both wild-type and mutant p53. PAb240 reacts exclusively with mutant p53. Fourteen LCLs reacted with PAb1801, but not with PAb240, suggesting that none of them expressed mutant p53. However, one LCL had mutant p53. This LCL differs from other LCLs in that it grows to higher cell densities and has a higher agarose clonability. All BLs expressed p53. Out of 15 BLs, nine (60%) carried mutant p53, as indicated by their reactivity with PAb240. Among the nine BLs with mutant p53, eight Epstein-Barr virus (EBV)-positive. Three out of the six BLs with wild-type p53 were EBV-positive. Multiple EBV-converted sublines all exhibited the same p53 status as the parental line. Our results indicate that the p53 gene is mutated in a majority of Burkitt lymphoma cell lines (BLs), and suggest that p53 mutation contributes to the malignant phenotype of these cell lines.