In order to assess the potential health effects of source water from the Yangtze River at Nanjing section, China, hepatic transcriptional profiles of male mice (Mus musculus) exposed to source water for 90 days were measured with Affymetrix Mouse Genome 430A 2.0 Array. A total of 585 gene expressions were significantly altered (1.5-fold, P < or = 0.05), including 298 up-regulated genes and 287 down-regulated genes. Among the identified genes, potentially important genes that may be implicated in the liver cancer were found, including VCAM 1, Dusp1, Cyp7a1, Egfr and Fhit. The source water exposure also resulted in significant aberration of gene expressions and biological pathways linking to xenobiotic metabolism, signal transduction, cell growth and death, immune/inflammation response and oxidative stress response. The results provide excellent insights into early toxic effects of the Yangtze River source water on human and environmental health.