Magnetization transfer contrast (MTC) in magnetic resonance imaging (MRI) is the result of selectively observing the interaction of bulk water protons with the protons contained in macromolecules of a tissue. Since different tissues have different macromolecular compositions, the MTC can generate very high tissue contrast that is based on well-defined physiochemical properties. This is accomplished by combining a saturation transfer technique with standard MRI procedures. The specific practical and theoretical aspects of saturation transfer as it applies to the generation of MTC are reviewed and discussed. In the last 3 years, MTC has been applied to the study of the body, with useful applications demonstrated in evaluating the morphology of the knee joint, eye, brain, breast, and heart. The application of MTC to accentuate MR angiography and contrast agent studies has also been demonstrated. Thus, MTC is becoming another tool towards maximizing the quality and diagnostic potential of MRI. Recent studies on isolated macromolecules have suggested that the MTC effect is specific to the surface chemistry and correlation time of the macromolecules. These latter results indicate that the magnetization transfer process may provide a unique quantitative method of MR tissue characterization based on macromolecule dynamics and chemistry.