During angiogenesis, endothelial cell (EC) proliferation is a critical event that contributes to development of the invasive pannus in rheumatoid arthritis (RA), as well as playing an important role in other angiogenesis-dependent pathological conditions. Proliferation in response to growth factors and mitogens requires an increase in the rate of protein synthesis in order to enter the G1 phase, and subsequently to proceed to S phase. The Ras-p42/p44 mitogen activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3K) signalling cascades play key roles in mediating this increase in protein synthesis. Two downstream signalling pathways have been described for PI3K. One pathway involves p70 S6 kinase. This is a serine/threonine kinase which controls multiple phosphorylation of the 40S ribosomal protein S6 and is activated by many mitogenic stimuli, including growth factors and cytokines. p70 S6 kinase can be distinguished from the other signalling pathway downstream of PI3K, Akt-GSK3, by its sensitivity to rapamycin, which is a potent inhibitor of p70 S6 kinase, preventing its phosphorylation and activation. This study analysed the contribution of PI3K-p70 S6 kinase in the control of vascular endothelial cell growth.