Rheumatoid arthritis (RA) is one of the most destructive inflammatory and autoimmune joint diseases, most frequently accompanied by extraarticular complications. The pathophysiologic mechanism and the importance of cell subpopulations in the initiation and perpetuation of synovitis are not sufficiently understood. In this study the frequency of lymphocyte subpopulations simultaneously in the synovial fluid (SF), the synovial membrane (SM) and peripheral blood (PB) of acute RA patients is determined, using flow cytometry procedures. The changes in the distribution of T lymphocyte subpopulations were significant on local levels in acute RA patients, resulting in a decreased CD4/CD8 ratio in SF, but an increased CD4/CD8 ratio in SM, compared to the ratio found in PB. The differences observed in the frequency of cells positive on natural killer (NK) cell markers suggest the role of CD16-CD56+ NK cell population in SF of RA patients. Significant differences in the observed frequency of lymphatic subpopulations suggest certain specificities of local immunological events in SM and SF in acute RA. These results confirm the T-lymphocyte hypothesis in initial pathogenic events in RA.