Tendinopathy is a significant clinical problem that can result from repetitive activity. While the precise etiology of this condition remains unclear, the cellular response to cyclical loading is believed to have a contributory role to the pathology of tendinopathy. This study examined the short-term biochemical response of avian flexor digitorum profundus tendon to repetitive cyclic loadings of varying magnitude. An in vitro tendon explant model was utilized to apply four levels of haversine tensile stress (peak stress of 0, 3, 12, and 18 MPa) at 1.0 Hz, 8 hr/day for 3 days. The 12 and 18 MPa levels were known to cause significant mechanical damage based on previous work. Tissue media was recovered and analyzed for prostaglandin E(2) (PGE(2)), lactate dehydrogenase (LDH, measure of cell death), and collagenase levels. Tissue samples were recovered and analyzed for cell viability, total collagen, and sulfated glycosaminoglycan content. Collagenase, LDH, and PGE(2) levels were found to be influenced by loading magnitude (p < 0.05) with higher levels being present at higher load magnitudes. Varying cyclical load magnitude caused minimal compositional changes as collagen content and glycosaminoglycan did not change. These results indicate that elevated cyclical mechanical loading of tendon quickly results in altered biochemical tissue responses indicative of tissue injury. More sustained cyclical loading over time may be required for these initial responses to induce more dramatic tissue changes as observed in clinical tendinopathy.