Methamphetamine (METH) is one of the most commonly abused psychostimulant, and is known to induce dopaminergic neurotoxicity by generating oxidative stress and free radicals. In the present study we investigated the effects of METH on egr-1 and c-fos immediate early gene induction in different regions of mouse brain, at different doses and different time courses. We also measured the tissue levels of monoamines in order to correlate their changes with gene expression. A single injection of METH (40 mg/kg) significantly increased egr-1 and c-fos mRNA expression within 30 min in frontal cortex, nucleus accumbens, caudate putamen, septum and CA1 region of hippocampus. Time course studies showed that in most cases, both genes were expressed within 30 min and decreased after 60 min. METH produced a significant decrease in striatal dopamine level, reaching a very low level after 24 h. Striatal serotonin level significantly increased and returned to control levels after 2 h. These data show that METH induced egr-1 and c-fos mRNA expression in selective brain areas, which correlated with an alteration in monoamines.