The effect of ionizing radiation on peritoneal macrophages of mice was investigated by means of the quantitative enzyme cytochemistry and the cyclic nucleotide immunocytochemistry. It was found that the activities of the lysosomal enzyme (AcPase and ANAE) and ATPase of macrophages were remarkably changed after the animals were irradiated (,60,Co γ-ray, 8 Gy). Further studies demonstrated that the specific immunofluorescence of cAMP and cGMP in macrophages was apparently influenced as compared with the control group. It is considered that ionizing radiation changes the structrue of membrane and enzyme proteins of macrophages by the cyclic nucleotide (cAMP and cGMP). The mechanism of the effect of ionizing radiation on macrophage will be further studied.