The objective of this study was to determine histologically the local and systemic soft tissue responses to polymeric particulate generated by mechanical degradation of prosthetic anterior cruciate ligament (ACL) devices in a canine model. Following gross observations at ligament retrieval, samples of synovial, meniscal, cartilage, and inguinal lymph node tissues were collected and processed for standard hematoxylin and eosin staining. Tissues within synovial capsules of stifle joints showed osteophytes and other osteoarthritic changes in response to all implant and control interventions. The particulate quantity and size distributions were determined using a computerized image analysis system, employing light and polarized light microscopy techniques. Particles generated from ACL devices elicited nondebilitating chronic synovitis in the joint capsule and a mild inflammatory response in inguinal lymph nodes for up to approximately one year in vivo. Statistically significant relationships were found between the particle quantity and tissue type, the size and tissue type, and the quantity and time in vivo.