Representational difference analysis (RDA) was used to compare gene expression in equine mononuclear cells either infected with equine herpesvirus-2 (EHV-2) or adsorbed with inactivated EHV-2. Seven clones identified in non-infected cells after three rounds of selective subtraction and enrichment for differentially expressed genes contained sequences homologous to equine monocyte chemoattractant protein 1 (MCP-1). This suggested that EHV-2 may down-regulate MCP-1 transcription in infected cells. These findings correlate well with similar findings described for human cytomegalovirus and support the view that EHV-2 may have the ability to modify the chemokine environment of infected cells. This may constitute an important feature of EHV-2 biology, because such an ability has the potential to compromise host defence mechanisms and predispose to infection with other pathogens.