A 16-20 h postirradiation incubation with caffeine enhanced X-ray killing of rodent and human cells. Cells tested were Chinese hamster ovary (CHO-K1), lung (CHL), V79, mouse L, HeLa S3, human fibroblasts (AF288, TC171, FS9 and CRL1166) and a human-hamster hybrid. The effect of caffiene on the X-ray survival curve of these cells was to remove the initial shoulder without significantly altering the mean lehtal dose (Do). This action was achieved at caffiene concentrations which of themselves cause less than 15% killing. In randomly growing CHO-K1 cells the caffeine-sensitive process occurs with a half-time of 2-5 h after irradiation. The existence in human and rodent cells of caffeine-inhibited genome repair of X-ray damage was found.