The knee is one of the most frequently injured joints in the human body. A recent study suggests that axial compressive loads on the knee may play a role in injury to the anterior cruciate ligament (ACL) for the flexed knee, because of an approximate 10 degrees posterior tilt in the tibial plateau (J. Orthop. Res. 16 (1998) 122-127). The hypothesis of the current study was that excessive axial compressive loads in the human tibio-femoral (TF) joint would cause relative displacement and rotation of the tibia with respect to the femur, and result in isolated injury to the ACL when the knee is flexed to 60 degrees , 90 degrees or 120 degrees . Sixteen isolated knees from eleven fresh cadaver donors (74.3+/-10.5 yr) were exposed to repetitive TF compressive loads increasing in intensity until catastrophic injury. ACL rupture was documented in 14/16 cases. The maximum TF joint compressive force for ACL failure was 5.1+/-2.1 kN for all flexion angles combined. For the 90 degrees flexed knee, the injury occurred with a relative anterior displacement of 5.4+/-3.8mm, a lateral displacement of 4.1+/-1.4mm, and a 7.8+/-7.0 degrees internal rotation of the tibia with respect to the femur.