The six-revolute-joint instrumented spatial linkage (6R ISL) is often the measurement system of choice for monitoring motion of anatomical joints. However, due to tolerances of the linkage parameters, the system may not be as accurate as desired. A calibration algorithm and associated calibration device have been developed to refine the initial measurements of the ISL’s mechanical and electrical parameters so that the measurement of six-degree-of-freedom motion will be most accurate within the workspace of the anatomical joint. The algorithm adjusts the magnitudes of selected linkage parameters to reduce the squared differences between the six known and calculated anatomical position parameters at all the calibration positions. Weighting is permitted so as to obtain a linkage parameter set that is specialized for measuring certain anatomical position parameters. Output of the algorithm includes estimates of the measuring system accuracy. For a particular knee-motionmeasuring ISL and calibration device, several interdependent design parameter relationships have been identified. These interdependent relationships are due to the configuration of the ISL and calibration device, the number of calibration positions, and the limited resolution of the devices that monitor the position of the linkage joints. It is shown that if interdependence is not eliminated, then the resulting ISL parameter set will not be accurate in measuring motion outside of the calibration positions, even though these positions are within the ISL workspace.