The use of magnetization transfer contrast (MTC) in magnetic resonance imaging of the human knee was evaluated in this study. MTC is generated by irradiating the macromolecular protons in tissue with a low power off-resonance radio-frequency field. This results in a decrease in water proton signal intensity where a tight magnetic coupling between water and macromolecules exists. With this approach, the authors have demonstrated that MTC can improve contrast in standard single-section, gradient-recalled-echo images of the knee with regard to fat-muscle and cartilage-synovial fluid comparisons. The effect of changes in repetition time, echo time, and flip angle were also quantitatively evaluated. More important, MTC was shown to generate useful cartilage-synovial fluid contrast on high-resolution three-dimensional images, in which contrast is difficult to generate. This approach may not only provide better structural information about the knee, but may also provide noninvasive insight into the structure and biochemical composition of cartilage in vivo.