The implication of apoptosis in the cytotoxicity of cadmium (Cd) on rat thymus, testicle and liver was investigated. Four days after Cd injection (1.5 and 3.0 mg/kg b.w. i.p) the testicle and thymus relative weight decreased but that of liver increased significantly in a dose-dependent manner. In vitro, 6 h incuba-tion of thymocytes in the presence of 10-3M Cd resulted in a typical degradation of DNA into oligonucle-otide fragments similar to that observed in the presence of the dexamethasone, suggesting the induction of apoptosis in the cells. The addition of 1 mM ZnSO4, a metallic antioxidant, prevented this fragmentation. Nick end-labeling method confirmed the involvement of apoptosis in the thymus and revealed a high per-centage of TUNEL-positive cells 48 h following Cd administration mainly in the cortical zone. An apoptot-ic effect was also observed in the testicle where TUNEL-positive cells were present, primarily in late stages of gametogenesis. In contrast, the liver of Cd-treated rats failed to exhibit significant levels of apoptosis and all hepatocytes showed strictly negative TUNEL-labeled nuclei. In contrast, centrilobular-necrosis was observed reflecting species differences in target cells. These findings suggest that the apoptotic mechanism in thymus and testicle, but not in liver, may contribute to the toxicity of cadmium in rats.