Polychlorinated biphenyls (PCB) exposure in rodents provides a useful model for the symptoms of Attention deficit hyperactivity disorder (ADHD). The goal of this study is to identify genes whose expression levels are altered in response to PCB exposure. The brains from 48 rats separated into two age groups of 24 animals each (4 males and 4 females for each PCB exposure level (control, PCB utero, and PCB lactational)) were harvested at postnatal days 23 and 35, respectively. The RNA was isolated from three brain regions of interest and was analyzed for differences in expression of a set of 27,342 transcripts. Two hundred seventy-nine transcripts showed significant differential expression due to PCB exposure mostly due to the difference between PCB lactational and control groups. The cluster analysis applied to these transcripts revealed that significant changes in gene expression levels in PFC area due to PCB lactational exposure. Our pathway analyses implicated 27 significant canonical pathways and 38 significant functional pathways. Our transcriptome-wide analysis of the effects of PCB exposure shows that the expression of many genes is dysregulated by lactational PCB exposure, but not gestational exposure and has highlighted biological pathways that might mediate the effects of PCB exposure on ADHD-like behaviors seen in exposed animals. Our work should further motivate studies of fatty acids in ADHD, and further suggests that another potentially druggable pathway, oxidative stress, may play a role in PCB induced ADHD behaviors. © 2011 Wiley Periodicals, Inc.