To clarify the natural course of synovitis after anterior cruciate ligament injury, we took synovial tissues at various periods after injury and analyzed them immunohistologically. Twelve patients with isolated anterior cruciate ligament injuries participated in the study. Inflammation intensity was graded semiquantitatively based on the following parameters: synovial lining cell depth, synovial hyperplasia, vascular hyperplasia, lymphocyte infiltration, and the expression of cell adhesion molecules. The expression of fibrogenic cytokines and the degree of fibrosis were also investigated to elucidate the mechanisms of arthrofibrosis. The results demonstrated that synovitis in the infrapatellar fat pad subsides within 3 months after injury with the progression of fibrosis. Fibrogenic cytokines, platelet-derived growth factor and transforming growth factor-beta, were detected at fibrotic sites, suggesting their involvement in arthrofibrosis. An increased incidence of arthrofibrosis recently has been recognized to occur when anterior cruciate ligament reconstruction is performed within several weeks after injury. We speculate that when anterior cruciate ligament reconstruction is performed during the stage of acute synovitis, the operation may further promote the synovitis, accelerating the arthrofibrotic reaction. Waiting to perform the anterior cruciate ligament reconstruction until the synovitis resolves may possibly decrease the motion problems seen postoperatively.