Hyaluronan (HA) is a key component of synovial fluid, responsible for hydrodynamic lubrication, synovial fluid conservation during flexion and cavity formation in embryos. Although HA is selectively retained in the cavity by the synovial lining (Sabaratnam et al., 2007), there is nevertheless a slow trans-synovial loss of HA. This is replaced by synthesis de novo by fibroblast-like synoviocytes facing the joint cavity. The aims were a] to measure apparent HA secretion rate and HA loss from rabbit knee joints in order to evaluate the loss-corrected secretion rate; b] to combine measurements of endogenous HA mass with the true secretion rate to evaluate intra-articular (i.a.) HA turnover time in vivo; c] to test whether HA secretion is coupled to joint movement. Knee joints of anaesthetized rabbits were cannulated. Endogenous HA mass mendog was harvested by 18x1ml washes with mixing cycles. Apparent secretion rate q_HA was measured by washouts 5h later. In other experiments the apparent loss over 5h was assessed. An order-of-magnitude greater mass of exogenous rooster or rabbit HA (I) was injected i.a in split doses every 30min for 5h, then the mass remaining at 5h (R) was determined by washout. HA mass and size were analysed by HPLC. Solution of the two simultaneous equations for the effects of loss on q_HA and of q_HA on apparent loss gave true secretion rate q_HAcorrected=I/(R- 5q_HA)and the true loss L=(I+5q_HAcorrected )-R. HA turnover time was then calculated as m_endog/q_HAcorrected. To test whether secretion was stimulated by movement, some of the above studies were repeated on joints cycled passively for 3min in every 15min over 5h. Apparent q_HA was 16.2±1.3µgh^-1 in static joints (n=34) and 30.9±2.6µgh^-1 in moved joints (n=25), i.e. movement stimulated HA secretion (p<0.05, unpaired t test). Apparent HA loss (I-R) was 46.4±6.0% (n=5) in static and 39.5±4.6% (n=5) in moved joints (p=0.38, unpaired t test). True HA secretion rates corrected for loss (q_HAcorrected)was 30.5±2.8µgh^-1 (n=34) and 61.9±5.6µgh^-1(n=25)in static and moved joints respectively. The mean m_endog was 468±24µg (n=59).Turnover time m_endog/q_HAcorrected was 17.1±1.4h (n=34) in static and 8.4±0.6h (n=25) in moved joints. Joint movement stimulated HA secretion, indicating that synovial lining cells show mechanosensitive secretion of HA. Turnover time for HA was much longer than the turnover time for intra-articular albumin and water (1-2h). This is in keeping with the known retention of HA by ultrafiltration by synovial lining extracellular matrix proteins (Sabaratnam et al., 2007). The estimates of HA loss and hence q_HAcorrected may be overestimates for normal joints because the injection of fluid increased fluid outflow, which increases trans-synovial HA flux.