Thirteen cell lines derived from human tumors of diverse tissue origin and histopathology were compared with 12 lines of normal skin fibroblasts with respect to chromatid damage induced by 25, 50, or 100 R of X-irradiation during the G2 period of the cell cycle. Only cells in metaphase were examined, and these had been irradiated 1.5 hr before fixation. When irradiated under identical conditions, the tumor cells showed significantly more chromatid breaks and gaps than did the normal cells at all doses tested. The data suggest that the increased G2 chromosomal radiosensitivity of the tumor cells is associated with deficient DNA repair during the G2-prophase period of the cell cycle.