Objectives: The cellular basis of painful tendon overuse pathology (tendinosis) is poorly understood. Due to close anatomic associations between mast cells and vessels in connective tissues, it has been postulated that mast cells may mediate the development of tendon hypervascularity or edema. Therefore, the purpose of this study was to examine the distribution of mast cells in men and women with patellar tendinopathy. <br> Design: Case control study.<br> Methods: Tendinopathic tissue was collected at open debridement of the patellar tendon, and control tendon from patients undergoing intramedullary nailing of the tibia. The tendon was assessed immunohistochemically by evaluating the distribution of mast cells (AA1), as well as markers for T-lymphocytes (CD3) and macrophages (CD68). The vessel area fraction was quantitated using computer-assisted digital image analysis.<br> Results: The prevalence of mast cells per mm2 [3.3 (3.0)] was greater in tendinosis tissue than in controls [1.1 (1.5)] (p=0.036). In tendinosis patients, mast cell density was moderately correlated with the vessel area fraction (r2=0.49) and with symptom duration (r2=0.52). <br> Conclusion: Mast cell prevalance in patellar tendinopathy was increased and was predominantly associated with vascular hyperplasia -- particularly among patients with longstanding symptoms. Future research should investigate whether mast cells play direct or indirect modulatory roles in the development and progression of human tendinosis.