Heritable variation in cellular radiosensitivity is believed to be an important determinant of normal tissue responses to radiation. There is increasing evidence that the initial level of DNA damage induced determines this cellular radiosensitivity. The superoxide dismutase genes have been shown to influence cellular radiosensitivity through their effects on free-radical damage. In this study we have examined the effect of inherited mutations in the Cu/Zn superoxide dismutase on DNA damage induction following ionizing radiation treatment. We have examined lymphoblastoid cell lines from normal individuals and patients with Familial Amyotrophic Lateral Sclerosis (FALS)--recently identified as having Cu/Zn SOD gene mutations. Radiation-induced DNA damage has been measured in these cell lines using pulsed-field gel electrophoresis (PFGE). A two-fold range of DNA damage induction was found between cell lines but this was unrelated to the mutations in the SOD1 gene. These data suggest that the SOD1 gene does not influence DNA damage induction but its influence on other aspects of cellular radiosensitivity require further evaluation. Despite the lack of correlation with Cu/Zn SOD mutations the wide range in DNA damage induction shown here has not been previously reported in lymphoblastoid cell lines and the implications of this on radiotherapy need to be considered.