OBJECTIVE AND DESIGN: The development of therapies directed against TNF alpha and IL-1 beta 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 TNF alpha and IL-1 beta. 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 TNF alpha and IL-1 beta. 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 TNF alpha and 2.4 for IL-1 beta), 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 TNF alpha and IL-1 beta, reflecting the distal signaling pathways shared by these cytokines. A large number of novel TNF alpha and IL-1 beta-regulated genes were identified. CONCLUSIONS: A panel of novel TNF alpha- and IL-1 beta-regulated genes was identified, and these are promising candidates for further study in relation to RA and other inflammatory diseases.