Numerous studies have focused on the significance of modern marker proteins in the synovial fluid of the knee joint and in the serum both, for osteoarthritis (OA) and rheumatoid arthritis (RA). The relationship between the serum concentrations and the concentrations in the synovial fluid is still unclear. Synovial fluid and serum samples were obtained from 13 patients with advanced OA and from 8 patients with severe RA and concentrations of MMP-1, MMP-3, MMP-13, TIMP-1, COMP and MIA/CD-RAP were determined. All values were normalized against the total protein concentrations. Serum concentrations of MMP-13 in the RA-group were statistically higher than the synovial values (P<0.05). MMP-13 was the only marker protein that revealed distinct higher levels in the serum than in the synovial fluid. The study design allows only conclusions about advanced stages of RA and OA. Longitudinal investigations may provide further information about the value of MMP-13 as a potential marker to monitor the course of RA and OA.