Several types of lymphoid and myeloid tumor cells are known to be relatively resistant to radiation-induced apoptosis compared to normal lymphocytes. The intracellular genera-tion of reactive oxygen species was measured in irradiated spleen cells from C57BL/6 and BALB/c mice and murine tu-mor cells (EL-4 and P388) by flow cytometry using dichlo-rodihydrofluoresceindiacetate and dihydrorhodamine 123 as fluorescent probes. The amount of reactive oxygen species generated per cell was low in the tumor cells compared to spleen cells exposed to 1 to 10 γ of gradiation. This could be due to the higher total antioxidant levels in tumor cells compared to normal cells. Further, the changes in mitochon-drial membrane potential and cytoplasmic C_a²⁺ content were appreciable in lymphocytes even at a dose of 1 Gy. In EL-4 cells, no such changes were observed at any of the doses used.About 65% of spleen cells underwent apoptosis 24 h after 1Gy irradiation. However, under the same conditions, EL-4 and P388 cells failed to undergo apoptosis, but they accu-mulated in G₂/M phase. Thus the intrinsic radioresistance of tumor cells may be due to a decreased generation of reactive oxygen species after irradiation and down-regulation of the subsequent events leading to apoptosis.