To determine the effect of cyclic strain amplitude and frequency on MMP-1 (interstitial collagenase) expression in tendon cells, rat tail tendons (RTT) were immobilized or cyclically displaced to various amplitudes (1, 3, or 6% strain at 0.017 Hz) or frequencies (1% strain at 0.017, 0.17, or 1.0 Hz) for 24 hr. Stress-deprivation for 24 hr resulted in a marked upregulation in MMP-1 expression. Cyclic tensile loading at 0.017 Hz was found to significantly inhibit, but not completely eliminate, MMP-1 expression at 1% strain. MMP-1 expression was completely eliminated at 3 and 6% strain. Increasing the frequency of application of the 1% strain to 0.17 or 1.0 Hz completely eliminated MMP-1 expression. Disruption of the actin cytoskeleton with cytochalasin D abolished all inhibitory effects of cyclic strain on MMP-1 expression. The results of our study demonstrate that MMP-1 expression in tendon cells can be modulated by varying amplitudes and frequencies of cyclic tensile strain, presumably through a cytoskeletally based mechanotransduction pathway.