This study investigated the use of dynamic, volumetric MRI to measure 3D skeletal motion. Ten healthy subjects were positioned on a MR-compatible knee loading device and instructed to harmonically flex and extend their knee at 0.5 Hz. The device induced active quadriceps loading with knee flexion, similar to the load acceptance phase of gait. Volumetric images were continuously acquired for 5 min using a 3D cine spoiled gradient-echo sequence in conjunction with vastly under-sampled isotropic projection reconstruction. Knee angle was simultaneously monitored and used retrospectively to sort images into 60 frames over the motion cycle. High-resolution static knee images were acquired and segmented to create subject-specific models of the femur and tibia. At each time frame, bone positions and orientations were determined by automatically registering the skeletal models to the dynamic images. Three-dimensional tibiofemoral translations and rotations were consistent across healthy subjects. Internal tibia rotations of 7.8±3.5° were present with 35.8±3.8° of knee flexion, a pattern consistent with knee kinematic measures during walking. We conclude that vastly under-sampled isotropic projection reconstruction imaging is a promising approach for noninvasively measuring 3D joint kinematics, which may be useful for assessing cartilage contact and investigating the causes and treatment of joint abnormalities.