Objective: The purpose of this work was to evaluate the results from sodium and proton magnetic resonance imaging (MRI) in detecting small changes in proteoglycan (PG) content in bovine articular cartilage specimens. Design: Articular cartilage from 15 specimens of bovine patellae were subjected to partial PG depletion with different concentrations of trypsin for 30 min. Sodium and proton MR images of the intact specimen were obtained on a 4T GE clinical MRI system. Two custom-built 7 cm-diameter solenoid coils tuned to proton and sodium frequencies were employed. Fast gradient echo and spin echo imaging sequences were used to determine sodium density, proton density and proton relaxation times (T-1 and T-1) of the specimens. Spectrophotometric assay was performed after MRI to determine PG concentrations of the cartilage specimens. Results: The sodium signal change correlated well with the observed PG loss (R-2=0.85. P<0.01) whereas the proton signal change was inconsistent (R-2=0.10, P<0.8). The change in proton T-1 and T-2 between the two regions did not correlate with PG loss (R-2=0.07 and R-2=0.06, respectively). Conclusions: Results from these studies demonstrate that sodium MRI is both sensitive and specific in detecting small changes in PG concentration, whereas proton density and relaxation properties are not sensitive to small changes in PG content. (C) 2000 OsteoArthritis Research Society International.