The primary site of inflammation in RA is the synovium, which undergoes infiltration by monocytes and T cells, with concomitant synovial cell proliferation. Characteristically there is an alteration in the density of blood vessels in the synovium. It is thought that the synovial neovascularisation perpetuates the inflammatory and destructive conditions in the developing lesion. VEGF plays a key role in both normal and pathological angiogenesis, and is involved in the pathogenesis of RA. CD40L, a member of the tumour necrosis factor (TNF) family, is expressed on activated T cells. Stimulation with CD40L-expressing cells or purified recombinant CD40L induces the secretion of pro-inflammatory cytokines, adhesion molecules and metalloproteinases. The effect of CD40L on the production of VEGF by cells present in RA synovium has not been addressed. To investigate whether CD40 ligation induces VEGF production from rheumatoid synovial cells and to analyse the mechanism of VEGF production in response to CD40 ligation.