Six-revolute-joint instrumented spatial linkages (6R ISLs) have become often-used devices to measure the complete six-degree-of-freedom motion of anatomical joints. Accuracy of motion measurement depends on ISL design and calibration technique. In this paper, a design process is outlined that uses computer graphics and numerical methods as aids in developing 6R ISLs that (i) physically assemble within the desired range of motion of the joint; (ii) do not collide with either the experimental apparatus or the subject joint; (iii) avoid singular linkage configurations that can cause forces to be applied to the joint; and (iv) measure selected anatomical motions most accurately. It is found that a certain subgroup of6R linkages are suitable for accurate measurement of specific motions, and can be the basis for new ISL designs. General guidelines are developed that can assist in the generation of unique linkage designs for different anatomical joints. The design process is demonstrated in the creation of an ISL to measure knee motion.