Thickening of the synovial membrane with proliferation of macrophage-like and fibroblast-like synoviocytes is observed in affected joints of rheumatoid arthritis (RA) patients, as well as extensive synovial infiltration of inflammatory cells. TNF plays a key role in driving the pathogenesis and persistence of RA. Blockade of TNF, using current biologics, has had profound therapeutic effects; nevertheless, between 30% and 40% of RA patients do not respond to this treatment. The mechanisms of response and nonresponse to biologic therapy remain unclear. p38 MAPK is present in the rheumatoid synovium and thought to play a role in the pathogenesis of RA, suggested by evidence that p38 is required for TNF-induced inflammatory processes. There are four p38 MAPK isoforms, α, β, γ and δ, which are found in varying levels in inflammatory cells. Although most research has to date focused on p38α, it has been demonstrated in the synovium that the functional protein produced from the L1 retrotransposable element can specifically induce p38δ. This suggests a possible second p38-mediated pathway of joint destruction in RA that may not be blocked by anti-TNF therapy. This study aimed to correlate the expression of p38δ in the rheumatoid synovium with clinical response and nonresponse to the anti-TNF biologic, infliximab (Remicade).