Rheumatoid arthritis synovial cells exposed to hypoxia express more proangiogenic activity. Rheumatoid arthritis (RA) synovial cells were exposed to either 21% oxygen (normoxia) or 1% oxygen (hypoxia) for 24 hours. Cell supernatants were filtered, and the protein fraction was resuspended in fresh medium. Angiogenesis in response to RA synovial cell supernatants was assessed after 11 days, using CD31 expression quantified by colorimetric assay. (a) Representative data, with cells exposed to either vascular endothelial growth factor (VEGF) (2 ng/ml), RA synovial cell supernatants or no stimulus. Data are means of triplicate determinations, and were analysed by one-way analysis of variance: ***P < 0.001. (b) Comparison of angiogenesis in response to normoxic and hypoxic RA synovial cell supernatants. Data are means of paired triplicate determinations for six separate patients, and were analysed by paired t-test: **P < 0.01. (c) to (f) Representative images showing morphology of the formed tubes stained for CD31 at day 11 (objective magnification, ×40): (c) untreated, (d) VEGF treated (2 ng/ml), (e) normoxic RA synovial cell supernatants and (f) hypoxic RA synovial cell supernatants from the same patient.