BACKGROUND Rotating hinge and mobile bearing tray knee replacement designs utilize a single fixed axis for tibial rotation, yet there is little published information regarding the natural internal-external axis (IEA) for tibial rotation. Identifying the IEA should provide an opportunity for reproducing normal knee kinematics and maintaining the balance of forces in the soft tissues that help control rotation of the tibia. METHODS The location and orientation of the IEA relative to the tibial plateau were calculated in 46 fresh frozen human cadaveric specimens using an instant center of rotation analysis at fixed knee flexion angles ranging from five degrees to 105°. RESULTS IEA location ranged from 4.0 to 4.9mm medial and 1.7 to 5.5mm posterior to the center of the tibial plateau (from 5° to 105° of knee flexion). IEA orientation was reported relative to a reference axis perpendicular to the plane of the tibial plateau. In the frontal plane, the IEA was not significantly different from the reference axis from five degrees to 45° flexion, and 2.0° to 2.7° valgus to the reference axis from 60° to 105° flexion. In the sagittal plane, the IEA was not significantly different from the reference axis from 5° to 15° flexion, and 3.0° to 7.0° extended from the reference axis from 30° to 105° flexion. CONCLUSIONS The IEA moves posteriorly with increasing knee flexion on the tibial plateau. Placement of the IEA relative to the tibial plateau for a rotating hinge or mobile bearing tray implant may represent a compromise between design objectives for moderate and deeper knee flexion. CLINICAL RELEVANCE This study has relevance for future knee implant designs.