The cosmopolitan coccolithophore Emiliania huxleyi forms frequent massive blooms and thus is important for global climate and the carbon cycle. Lytic viral infection of this alga leads to termination of blooms and therefore influences global climate. To understand the host-virus interaction of E. huxleyi an expressed sequence tag (EST) approach was used to determine changes in gene expression during viral infection. Three cDNA libraries, generated 6, 12 and 24 h after viral infection, were compared to a library from an uninfected culture by sequencing, clustering and manual annotation of 1100-1500 ESTs per library. To verify the gene expression results of the ESTs we used two-colour oligonucleotide microarrays. A total of 4480 ESTs were assembled into 1871 clusters, of which, 223 are of viral origin. Microarray expression analysis indicated that 231 out of 565 oligonucleotides of E. huxleyi changed their expression level for at least at one time point in response to viral infection. Results suggest that viral infection affects the following processes: photosynthesis, transcription and translation, carbohydrate and lipid metabolism (particularly glycolysis), metabolism, and signal transduction. Results of this study provide insights into the gene expression of E. huxleyi during infection by the virus EhV-86. © 2010 British Phycological Society.