Obejctive and Design: The development of therapies directed against TNFa and IL-1b has underscored the importance of these cytokines in rheumatoid arthritis (RA). In this study, oligonucleotide microarrays were used to identify novel transcriptional events mediated by TNFa and IL-1b. Methods: In this study we have used Affymetrix U95A GeneChips representing 12,600 full-length human genes to identify transcriptional events mediated by these cytokines. Fibroblast-like synoviocytes were cultured from rheumatoid synovium from RA patients and stimulated with TNFa and IL-1b. Gene transcript levels were determined using Affymetrix U95A GeneChips representing 12,600 full-length human genes. Results: A large number of differentially regulated genes were identified (1.7% of array-displayed genes for TNFa and 2.4% for IL-1b), and the validity of the array protocol was subsequently confirmed using real-time PCR. The majority of the differentially expressed genes were regulated by both TNFa and IL-1b, reflecting the distal signaling pathways shared by these cytokines. A large number of novel TNFaand IL-1b-regulated genes were identified. Conclusions: A panel of novel TNFa- and IL-1b-regulated genes was identified, and these are promising candidates for further study in relation to RA and other inflammatory diseases.