Synovitis of recent onset is a challenging problem, both from a diagnostic and a mechanistic point of view. The role of the immune system in mediating the systemic and synovial inflammatory response remains an area of active investigation. Studies in early synovitis cohorts have confirmed the relatively specific association of rheumatoid factor positive polyarthritis with a number of autoantibodies, particularly anticyclical citrullinated peptide (CCP) antibodies, antifilaggarin antibodies (AFA), and anti-Sa antibodies. Immunopathologic studies of synovial tissue samples from patients with early synovitis have generally suggested quantitative rather than qualitative differences between various forms of synovitis. In particular, Th1 cytokines appear to predominate in rheumatoid arthritis and psoriatic synovitis, while Th2 cytokines are more often detectable in the synovium of reactive arthritis patients. This latter observation is consistent with an immune response profile that favors persistence of intracellular organisms.