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Current noninvasive or minimally invasive methods for evaluating in vivo knee kinematics are inadequate for accurate determination of dynamic joint function due to limited accuracy and/or insufficient sampling rates. A three-dimensional (3-D) model-based method is presented to estimate skeletal motion of the knee from high-speed sequences of biplane radiographs. The method implicitly assumes that geometrical features cannot be detected reliably and an exact segmentation of bone edges is not always feasible. An existing biplane radiograph system was simulated as two separate single-plane radiograph systems. Position and orientation of the underlying bone was determined for each single-plane view by generating projections through a 3-D volumetric model (from computed tomography), and producing an image (digitally reconstructed radiograph) similar (based on texture information and rough edges of bone) to the two-dimensional radiographs. The absolute 3-D pose was determined using known imaging geometry of the biplane radiograph system and a 3-D line intersection method. Results were compared to data of known accuracy, obtained from a previously established bone-implanted marker method. Difference of controlled in vitro tests was on the order of 0.5 mm for translation and 1.4° for rotation. A biplane radiograph sequence of a canine hindlimb during treadmill walking was used for in vivo testing, with differences on the order of 0.8 mm for translation and 2.5° for rotation.