Magnetization transfer (MT) and T(1) and T(2) relaxation of normal, trypsinized, and interleukin-1beta (IL-1beta)-treated cartilage were measured in the absence and presence of Gd-DTPA(2-). Without the addition of Gd-DTPA(2-), neither T(1) nor T(2) showed any significant change with cartilage damage. However, with Gd-DTPA(2-), trypsinized cartilage exhibited substantially shorter T(1) than normal cartilage, as expected due to the glycosaminoglycan (GAG) loss in these samples, and associated increased Gd-DTPA(2-) concentration. The T(2) results were similar, but less dramatic. The MT pseudo first-order exchange rate, RM(0B), did not depend on the contrast agent concentration, as expected, and was significantly faster for trypsinized and slower for IL-1beta-treated cartilage. In both cases, the MT fraction of the macromolecular pool M(0B) decreased while only trypsinized cartilage showed an increase in MT exchange rate R. The MT ratio (MTR) decreased with increasing Gd-DTPA(2-) concentration. However, interpretation of the MTR results in the presence of Gd-DTPA(2-) was complicated due to competing effects of increased longitudinal relaxivity and MT exchange. Therefore, in a cartilage sample with an unknown degree of GAG depletion and some collagen damage, a full MT analysis might be used to probe the molecular state of cartilage, but it would not be possible to use a simple MTR measurement after the administration of Gd-DTPA(2-) to differentially determine the amount of cartilage degradation in the sample.