Introduction. Hyaluronan (HA) regulates trans-synovial fluid drainage and aids joint lubrication. HA secretion (q_HA) is stimulated by joint movement (Wann et al, this meeting), in keeping with its arthro-protective role. Here we tested the hypothesis that movement-stimulated q_HA is a graded response affected by movement duration and/or cycle frequency. We also tested whether movement-stimulated HA secretion (MSHA) requires transcription-translation. Methods. Endogenous HA was washed out from cannulated knee joints of anaesthetised rabbits. The joint was left for 5h, either static or moved, then the secreted HA was recovered by further washouts. HA was analysed by HPLC. Moved joints were cycled passively at 0.5Hz for 0, 7%, 20% or 60% of the secretion period in the pattern 0, 1, 3 or 9 min in every 15min for 5h. In a second series joints were cycled for 20% duration (3/15 min) at 0, 0.17Hz, 0.5Hz or 1.5Hz. To investigate whether MSHA requires de novo protein synthesis, moved joints injected with cycloheximide (CX, 0.36mM) were compared with paired, Ringer-injected moved joints. As positive controls, q_HA was measured in static joints stimulated by phorbol-12-myristate-13-acetate (PMA, 0.35mM) in the presence or absence of CX. In a further study moved joints were injected with actinomycin-D (AD, 11mM) and puromycin (PM, 0.3mM) to block both transcription and translation. Results. Since joints vary in size, q_HA was normalised per 100 mg endogenous HA (%q_HA). The %q_HA varied with the duration of movement, falling significantly from 7.82±0.52 mg h^-1 (100 mg)^-1 (± sem) at 60% duration (n=5) and 7.93±0.50 mg h^-1 (100 mg)^-1 at 20% duration (n=19) to 5.29±0.25 mg h^-1 (100 mg)^-1 at 7% duration (n=5) and 3.65±0.27 mg h^-1 (100 mg)^-1 in static joints (n = 24) (p=0.02, 1-way ANOVA). Cycle frequency increased %q_HA from 4.87±0.49 mg h^-1 (100 mg)^-1 in joints moved at 0.17 Hz to 7.27±0.63 mg h^-1 (100 mg)^-1 in joints moved at 1.5 Hz. (p=0.014, n=6 pairs, paired t-test). Inhibition of translation by CX had no significant effect on MSHA (CX moved, 7.79±1.55 mg h^-1 (100 mg)^-1; Ringer moved, 9.37±2.21 mg h^-1 (100 mg)^-1) (p=0.12, n=5 pairs, paired t test). In positive controls CX reduced PMA stimulated %q_HA from 13.17±2.57 mg h^-1 (100 mg)^-1 to 6.40±0.97 mg h^-1 (100 mg)^-1 (n = 3 pairs). As with CX, AM+PM-treated moved joints showed no reduction in %q_HA (p=0.29, n=5 pairs, paired t test). Discussion. HA secretion is stimulated by joint movement in a graded fashion, dependent on the duration and frequency of joint movement. The mechanosensitive transduction process was not dependent on transcription-translation.