Cadmium (Cd) induces apoptosis in vitro and in vivo. However, the mode of action is unclear. Cytochrome C (Cyt c) release from mitochondria into cytoplasm is a key event in apoptosis. In this study, we examined the effects of Cd on the release of Cyt c from mitochondria using human leukemia HL-60 cells and isolated mitochondria. Cd induced apoptosis in HL-60 cells in a dose-dependent manner, in accordance with increases in cytosolic Cyt c. Cd at 25 μM also induced the release of Cyt c from isolated mitochondria. Mitochondrial swelling induced by permeability transition is known to cause outer membrane rupture and Cyt c release from mitochondria. Cd induced a swelling of mitochondria in vitro, as did calcium, a classical inducer of mitochondrial permeability transition. These results suggest that apoptosis induced by Cd appears to be involved in a mitochondria-dependent pathway and in the release of Cyt c from mitochondria by swelling.