Abstract: The present study was designed to investigate the effect of selenium (Se) administration (as sodium selenite: 0.5 or 1 mg kg-1 body weight) or/and α-difluromethylornithine (DFMO: 2 mg kg-1 body weight) on the elevated polyamine levels. For this purpose the polyamine (putrescine, spermidine, spermine) levels were elevated in female Swiss albino mice by adding 2% of both L-arginine and L-ornithine to the drinking water for four weeks. The elevated putrescine and spermidine levels were decreased significantly by administration low and high dose of Se. The DFMO abolished the concentrations of both putrescine and spermidine in liver and kidney of the experimental mice. The combination of Se and DFMO normalized the polyamine levels. On the other hand, the spermine level was increased in liver and kidney by administration of Se or/and DFMO. To elucidate the effects of the elevated polyamines on the oxidative enzymes, the activity of glutathione peroxidase (GSH-PX), glutathione reductase (GSH-R) and superoxide dismutase (SOD) in the liver and the kidneys of the experimental mice were determined. The GSH-Px, GSH-R and SOD activities were increased by Se administration compared to the control. Conversely, DFMO produced an inhibition in the activity of antioxidative enzymes. These results suggest that the combination between Se and DFMO appear to be additive chemopreventive effect to reduce the elevated polyamine levels. This combination will protect the tissues from the deleterious effect of high polyamine levels and improve the activities of the cellular antioxidative system.