Gene expression changes are candidate mechanisms to contribute to long-term consequences of psychostimulant use. We use microarrays to examine the expression of 6340 genes in brains of mice killed 5 or 20 h following 14 day, twice-daily treatments with saline (SS), saline followed by a single 7.5 mg/kg amphetamine dose (SA), or repeated 7.5 mg/kg amphetamine doses (AA) that produce sensitization but no clear-cut neuronal toxicities. Arrays display robust hybridization for about 3600 transcripts. One hundred and seventeen of these expressed transcripts are candidate positives for drug-related changes, displaying > 1.8-fold differences from SS control values in whole brains of either SA or AA mice. Five transcripts reveal altered expression in both AA and SA mice. SA mostly enhances expression while AA treatments largely reduce expression. Fourteen SA and four AA changes in whole brain mRNA were replicated by > 1.8-fold changes in independent microarray assessments of either cerebral cortical or brainstem mRNAs, with more changes identified in frontal than in entorhinal/parietal cortical samples. About one-quarter of these changes persist in initial studies of mice killed 20 h after the last amphetamine injection. Each of these genes, including transcription factor, cellular regulatory, structural and other gene family members, are candidates to contribute to brain adaptations to psychostimulants.