Recently described DNA microarray technology allows parallel screening of expression patterns and regulation of hundreds of thousands of genes. In the present study, we used a microarray to examine the gene expressions in the midbrains of mice sacrificed 24 h after completion of a 7-day treatment period consisting of a once-daily treatment with saline (SS), saline followed by a single 2 mg/kg of body weight dose of methamphetamine (METH) (S-METH), or repeated 2 mg/kg METH doses (M-METH) that produced sensitization and place preference (rewarding effect). We used the commercially available cDNA microarray. Approximately 80 % of the assessed transcripts in the total brain reached the Affymetrix criteria for "present" and "changed," as well as displaying greater than or equal to 1.5-fold differences in hybridization intensity difference values in a comparison of SS data to S-METH or M-METH data. S-METH gene expression changes were observed in both up- and downregulation, with 13 transcripts upregulated and 13 downregulated, whereas the majority of M-METH gene expression changes were observed in downregulation, with 5 transcripts upregulated and 21 downregulated. We identified several genes that altered expression in both the S-METH and M-METH groups: a transcription factor gene, cellular stress/molecular chaperones, and a cellular regulatory gene.