Freshly isolated synovial fluid (SF) and plasma samples from 20 patients with rheumatoid arthritis (RA) and 9 patients with joint effusions of other diagnoses (non-RA) were immediately (without fractionation or dilution) used as a culture medium for murine articular cartilage. Both intact SF, and cell depleted SF were tested for the effect on proteoglycan synthesis (35S-incorporation) compared to the patients' plasma or standard tissue culture medium. In addition, the effect on proteoglycan degradation was measured using 35S-prelabeled cartilage. Intact SF and cell depleted SF were found to suppress chondrocyte metabolism both in the RA and non-RA group. In the group with RA a strong correlation was found between the number of cells in SF and the degree of suppression. In the same group, intact SF caused a markedly higher suppression of chondrocyte biosynthesis than in the non-RA group (p less than 0.02). In general, the suppressive effect of SF appeared to be at least partially related to inflammatory activity (number of cells in SF) rather than a specific feature of RA. During the short term exposure, no measurable breakdown of matrix proteoglycan was found, both in complete SF and cell depleted SF. Mechanistic studies suggest that neither hydrogen peroxide generated by polymorphonuclear neutrophil leukocytes nor variations in SF viscosity were responsible for the observed effects.