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The objective of the current study was to use fluoroscopy and computed tomography to accurately determine the three-dimensional, in vivo, weightbearing kinematics of five normal knees. Three-dimensional computer-aided design models of each subject’s femur and tibia were recreated from the three-dimensional computed tomography bone density data. Three-dimensional motions for each subject then were determined for five weightbearing activities. During gait, the lateral condyle experienced −4.3 mm (range, −1.9–−10.3 mm) of average motion, whereas the medial condyle moved only −0.9 mm (range, 3.4–−5.8 mm). One subject experienced 5.8 mm of medial condyle motion. On average, during deep flexion activities, subjects experienced −12.7 mm (range, 1.4–−29.8 mm) of lateral condyle motion, whereas the medial condyle motion only was −2.9 mm (range, 3.0–−9.0 mm). One subject experienced 5.8 and 9.0 mm of medial condyle motion during gait and a deep knee bend, respectively leading to the occurrence of a lateral pivot motion. During the deep flexion activities, the subjects experienced significantly more axial rotation (> 13°) than gait (< 5°). During all five activities, the lateral condyle experienced significantly more anteroposterior translation, leading to axial rotation of the tibia relative to the femur.