OBJECTIVE: To determine the responses of the medial and lateral collateral ligaments (MCL, LCL) of the human knee to externally applied stresses. DESIGN: Differential variable reluctance transducers were used to measure length changes along the long posterior parallel fibers of the MCL and the middle third of the LCL through a flexion range of 15-120 degrees and a variety of external stresses. BACKGROUND: There is a lack of consensus regarding the collateral ligament response to internal and external tibial rotation. In addition, there are very few studies that have investigated the effects of quadriceps and hamstrings muscle group loads on the strain in the collateral ligaments. METHODS: Three series of tests were performed. First, the passive behavior of the ligaments was obtained as well as the ligament response to 3 degrees of varus and valgus rotation. The next series tested the ligaments' response to 0-10 degrees of internal and external tibial axial rotation. Finally, isolated and co-contracted quadriceps and hamstrings muscle group loads were applied. RESULTS: The instrumented portions of both ligaments were more strained in extension than flexion. Varus rotations stretched the LCL, whereas valgus rotations elongated the MCL. The strain in the MCL was shown to increase during external rotation and decrease during internal rotation. The LCL did not exhibit a uniform response across specimens to internal or external tibial axial rotation, but was consistent between left and right knees from a single cadaver. Highly consistent trends of interactions between muscle loads and the strain in both the MCL and LCL were noted. CONCLUSIONS: The responses of the MCL and LCL to applied stresses are dependent upon the flexion angle of the knee, the influence of muscle loading and, to a lesser extent, anatomic variation in the ligaments themselves. Guidelines for rehabilitation of the collateral ligaments following injury are suggested.