Background. Due to direct contact with cartilage, bone surface and synoviocytes, the study of synovial fluid in rheumatoid arthritis has a great diagnostic value, and changes in its indicators clearly correlate with the data of the morphological study of the affected articular tissues. In the synovial fluid of rheumatoid arthritis patients, protein substances of diffe-rent molecular mass and enzymes involved in the destruction of cartilage, tendons and ligaments are accumulated. At the same time, there are no reliable differential diagnostic biomarkers of synovial fluid in joint pathology. The purpose and objectives of the study: to establish the clinical and pathogenetic significance of medium molecular weight compounds of different fractions in the synovial fluid of patients with rheumatoid arthritis, the relationship with physicochemical disorders in the synovial fluid and the composition of surfactants in it. Materials and methods. The synovial fluid obtained from the knee, elbow and shoulder joints was studied in 21 patients with rheumatoid arthritis (mean age 50 years, male to female ratio of 1 : 2), among whom mo-derate and high degree of disease activity was established in all cases, III and IV stages of pathological process — in 61.9 %, extra-articular form of the disease — in 61.9 %, systemic osteoporosis — in 95.2 %, seropositivity for rheumatoid factor (RF) — in 90.5 %, for cyclic citrulline peptide antibodies (CCPA) — in 95.2 % of patients. To determine the middle mass molecules in the synovial fluid and blood serum, a screening method was used with trichloroacetic acid precipitation of proteins and determination of the light absorption spectra by the acid-soluble fraction. Protein and non-protein nitrogenous surfactants were studied using an Olympus-AU640 bioanalyzer (Japan), and interfacial tensiometry with calculating the surface tension ratio at an infinite surface lifetime for high molecular weight substances and at a time of 0.01 s for low-molecular weight compounds (ST∞/0,01 %) was carried out using a computer apparatus ADSA-Toronto (Germany-Canada). Results. The integral composition of medium molecular weight compounds in synovial fluid and blood depends on serum levels of RF and CCPA, and the rates of progression of articular syndrome are associated with indicators of nucleotide (NF) and chromatophore fractions (CF) of middle mass molecules, which, along with aminopeptide (AF) and peptide fractions (PF), determine the high activity of the dise-ase, bone-destructive changes in the joints (AF), bone mineral density (AF, PF, CF), the formation of bone erosions (AF) and intra-articular chondromic bodies (NF, CF), directly correlate with the content of immunoglobulin G in the synovial fluid (NF, CF), and CF is directly correlated with the presence of arthrocalcifications and Hoffa’s fat pads. Conclusions. In rheumatoid arthritis, middle mass molecules of different fractions in the synovial fluid are involved in the disease pathogenesis, depend on clinical, radiological and sonographic signs of the disease, can be used to predict the course of the pathological process.