A series of experiments showed that, on exercise of the inflamed human knee, intra-articular pressure rises above synovial capillary perfusion pressure, causing intra-articular hypoxia; and that, on cessation of exercise, there is oxidative damage to lipids and IgG within the joint. These findings are consistent with the hypothesis that persistence of synovial inflammation can be due to exercise-induced hypoxic-reperfusion injury mediated by reactive oxygen species.