Both the G2 chromosomal radiosensitivity assay and allelic differences in TP53 codon-72 have been associated with cancer predisposition. The relationship between the two endpoints was determined in 56 human EBV-transformed lymphoblastoid cell lines. Although there were overlapping distributions of sensitivity for the different genotypes, cell lines that were homozygous for the proline coding allele were more likely to be resistant to chromatid break formation than those containing two arginine coding alleles, whereas cell lines expressing both the proline and arginine codon were either resistant like proline-proline lines or sensitive like arginine-arginine lines. The results support an important role of the TP53 codon-72 polymorphism in modifying G2-chromosome radiosensitivity. Distinguishing the effect of TP53 codon-72 variations from other modifiers of G2-chromosome radiosensitivity might aid in identifying new markers of cancer risk.