Reactive oxygen species (ROS) are involved in a number of disease states where they are believed to be responsible for cellular damage. In this study we examined the effect of ROS generation on polyamine catabolism. Treatment of human breast cancer cells with either H2O2 or hyperoxia increased the activity of spermidine/spermine N1-acetyltransferase (SSAT). These increases occurred before any significant signs of cellular injury. Agents known to decrease the production of reactive oxygen species such as dimethylthiourea and o-phenanthroline prevented the increase in SSAT activity indicating ROS involvement in the induction process. These results suggest that induction of SSAT may be a protective response to oxidative stress in mammalian cells facilitating removal of polyamines from the cell to prevent their toxic accumulation.