Tomato (Solanum lycopersicon), a model species for the family Solanaceae, is severely affected by Tomato spotted wilt virus (TSWV) worldwide. To elucidate the systemic transcriptional response of plants to TSWV infection, microarray experiments were performed on tomato. Parallel analysis of both shoots and roots revealed organ-specific responses, although the virus was present in similar concentration. In the shoots, genes related to defense and to signal transduction were induced, while there was general repression of genes related to primary and secondary metabolism as well as to amino acid metabolism. In roots, expression of genes involved in primary metabolism and signal transduction appear unaffected by TSWV infection, while those related to the response to biotic stimuli were induced and those associated to the response to abiotic stress were generally repressed or unaltered. Genes related to amino acid metabolism were unaffected, except for those involved in synthesis of secondary compounds, where induction was evident. Differential expression of genes involved in metabolism and response to ethylene and abscisic acid was observed in the two organs. Our results provide new insight into the biology of the economically important interaction between tomato and TSWV.