Actively growing V79 Chinese hamster [lung] cells, treated with anisotonic phosphate-buffered saline (PBS) after X irradiation, are more sensitive than cells treated with isotonic PBS or cells promptly incubated with complete medium immediately after irradiation. The anisotonic PBS solutions used were not toxic to unirradiated cells. The sensitization of irradiated cells results from hypotonic as well as hypertonic NaCl concentrations in PBS, is strongly dependent on both temperature and time, and is mainly due to an increase in the final slope of the single-dose survival curve. Cells at essentially all ages in the division cycle are sensitized. The oxygen-enhancement ratios of cells receiving an anisotonic or an isotonic post-treatment are almost equal and suggest that typical radiochemically induced lesions, rather than nonspecific stress, are involved in the enhanced lethal response. After 2 X-ray dose fractions, the net response of cells sensitized after each fraction by anisotonic post-treatment is similar to that obtained for isotonically treated cells and indicates that sublethal damage repair is not influenced by the enhanced expression of lethal damage. Independence of the repair of damage which is potentially lethal from the repair of damage which is sublethal is further suggested by the more rapid rate of the former compared to that of the latter. In contrast to the modification of expression of potentially lethal damage in plateau phase cells, following lethal exposures to nonionizing radiations with or without the prior incorporation of 5-bromodeoxyuridine into DNA, essentially no additional damage is expressed by the anisotonic PBS treatment of actively growing cells. Thus, essential differences in the molecular bases of cell killing by nonionizing vs ionizing radiation are suggested. The proposal is advanced that the enhanced expression of damage which, after X irradiation, can be shown to be potentially lethal results from a destabilization of the structural relationship between DNA and the nuclear envelope, and/or DNA and the nuclear protein matrix, as a consequence of osmotic changes produced by anisotonic treatment.