We describe a typical case of a patient with remitting seronegative symmetrical synovitis and pitting edema (RS(3)PE) syndrome. He underwent a successful clinical course monitored by serologic variables and radiographic methods. Serum levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 and serum amyloid A were remarkably elevated. Accumulation of inflammatory cells into the multiple joints was found by gallium-67 scintigraphy. Multiple and symmetrical tenosynovitis with hypervascularity in the presence of subcutaneous edema of the hands and feet were determined by magnetic resonance imaging (MRI) and ultrasonography. These serologic and radiographic abnormalities immediately improved after treatment with a low-dose steroid. Our present case supports a previous observation that synovial tissue is a major inflammatory source of RS(3)PE syndrome. IL-6 (and VEGF), probably produced from the synovial tissues, are considered to be essential factors in the development of RS(3)PE syndrome.