Polyomavirus BK-associated nephropathy (PVAN) is an emerging cause of early renal transplant failure. In order to learn more about the cellular response to BK virus, microarrays were used to study its effect on mRNA expression in human endothelial cells. The oligo-based, 35k arrays used cover the predicted 25,000 human protein-expressing genes, and distinguish between a number of alternatively spliced mRNAs. Four parallel experiments were performed for each of two time-points (24 and 40 h) during the first round of the 48 h viral replicative cycle. Immunoperoxidase staining demonstrated that the pulse exposure to virus caused infection in at least 75% of the cells. At 24 h, 55 genes were more than doubly up-regulated and 249 genes were similarly down-regulated; at 40 h, the numbers were 242 and 104, respectively. Gene ontology analyses suggested that immune/defence response genes were selectively down-regulated. Genes involved in cell division and DNA replication tended to be up-regulated, which may reflect an attempt on behalf of the virus to promote viral replication. Genes associated with PVAN were not induced, suggesting that these genes are not required for viral replication, but rather reflect circumstances specific for the disease. Only a few immuno-related genes were turned on, including the interferon response genes G1P2 and IFIT3. However, some of the up-regulated genes of unknown function may be involved in viral defence.