Amphetamine is a neurotoxic psychostimulant that causes dopamine depletion and neuronal death in the rodent striatum. In the present study, we sought to determine if toxic doses of the drug can also induce pathological changes in the mouse olfactory bulb. We found that injections of amphetamine (10 mg/kg x 4, given 2 h apart) caused significant decreases in dopamine levels in that structure. This dose of the drug also induced substantial increases in the number of terminal deoxynucleotidyl transferase-mediated deoxyribonucleotide triphosphate (dNTP) nick end labeling (TUNEL)-positive cells in the olfactory bulb indicative of elevated DNA fragmentation. These results show that the toxic effects of amphetamine involve the olfactory bulb in addition to the striatum. These observations need to be taken into consideration when discussing the clinical course of amphetamine addiction.