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We utilized oligonucleotide microarrays and subsequent gene set enrichment analysis (GSEA) to assess patterns of gene expression changes in male largemouth bass (<jats:italic>Micropterus salmoides<\/jats:italic>) hepatic tissues after a 96\u2009h exposure to common environmental contaminants. Fish were exposed to atrazine, cadmium chloride, PCB 126, phenanthrene and toxaphene via intraperitoneal injection with target body burdens of 3.0, 0.00067, 2.5, 50 and 100\u2009\u00b5g\u2009g<jats:sup>\u22121<\/jats:sup>, respectively. This was conducted in an effort to identify potential biomarkers of exposure. The expressions of 4, 126, 118, 137 and 58 mRNA transcripts were significantly (<jats:italic>P<\/jats:italic> \u2264 0.001, fold change \u22652\u00d7) affected by exposure to atrazine, cadmium chloride, PCB 126, phenanthrene and toxaphene exposures, respectively. GSEA revealed that none, four, five, five and three biological function gene ontology categories were significantly influenced by exposure to these chemicals, respectively. We observed that cadmium chloride elicited ethanol metabolism responses, and along with PCB 126 and phenanthrene affected transcripts associated with protein biosynthesis. PCB 126, phenanthrene and toxaphene also influenced one\u2010carbon compound metabolism while PCB 126 and phenanthrene affected mRNA transcription and mRNA export from the nucleus and may have induced an antiestrogenic response. Atrazine was found to alter the expression of few hepatic transcripts. This work has highlighted several biological processes of interest that may be helpful in the development of gene transcript biomarkers of chemical exposure in fish. 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