This report reviews and discusses studies on the synovial fluid and biopsy specimens of synovial membrane obtained during the first 6 weeks of synovitis that evolved into rheumatoid arthritis (RA). Five previously unreported cases are described. Early changes in the microvasculature and synovial lining seem to antedate the classical chronic inflammation of established RA. Further characterization in the joint tissues in very early RA offers opportunities for identification of exogenous triggers and may allow more appropriate targeting of early therapy to potentially reversible aspects of pathogenesis.