Aims: The purpose of this study is to examine the relationship between synovitis and shoulder pain in rotator cuff disease. Methods: Thirty-nine patients with rotator cuff disease were candidates. Subacromial synovium around the greater tuberosity and glnohu-meral synovium around the rotator interval were harvested for specimens during operation. The expression levels of inflammatory cytokine mRNA of interleukin-1β and its naturally occurring antagonists (secreted and intracellular interleukin-1 receptor antagonists) were measured by reverse transcription plolymerase chain reaction (RT-PCR). The cytokine-mRNAs producing cells were identified by RT- in situPCR. For control specimens, subacromial bursae were obtained from 10 patients with anterior instability of the shoulder that exhibited no signs of subacromial impingement. All specimens were obtained with patient’s informed consent. The level of shoulder pain was evaluated in each patients before the operation with a visual analogue scale: 0 as no pain, 5 as moderate, and 10 as severe. Results:The expression levels of the cytokine-mRNAs in the subacromial bursa well correlated to the level of shoulder pain, but not those in the glenohumeral joint. A variety of the cells (synovial and inflamatory cells) produced the cytokines at the protein and gene level in both subacromial and glenohuemeral synovium. Conclusions: Subacromial bursa is the site associated the shoulder pain caused by rotator cuff disease, and targeting the subacromial bursa for treatment leads to successful pain relief in patients with the disease.