Cytotoxic effects of desipramine on human colon carcinoma HT29 and HCT116 cells were examined. Desipramine reduced the viability of HT29 cells in a concentration-dependent manner, but failed to cause any significant change in the viability of HCT116 cells by the concentration up to 50 µmol/l, at which an approximately 60% reduction of the viability of HT29 cells was observed. Despite their different sensitivities, desipramine caused the nonoxidative apoptotic damage to both of them. In contrast to HT29 cells, desipramine might cause the apoptotic death of HCT116 cells through the disturbance of mitochondrial function. These results suggest that desipramine may cause the nonoxidative apoptotic damage to different types of human colon carcinoma cells through either a nonmitochondrial or a mitochondrial pathway, which may confer the different sensitivities to this drug on these tumor cells.