OBJECTIVE To examine the precise tissue distribution of dendritic cells (DC) and indoleamine 2,3-dioxygenase (IDO)-expressing cells in synovial tissue and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS Synovial tissues from 30 patients with RA and 7 with OA were immunohistochemically stained for DC markers. The examined areas were classified into 5 categories based on pathobiological staging and histopathological grading systems. Myeloid DC (mDC) and plasmacytoid DC (pDC) were isolated using positive and negative magnetic sorting systems, respectively, from SF samples (7 patients with RA and 4 with OA) and synovial tissues (3 RA, 4 OA). RESULTS mDC were mainly observed in lymphoid aggregations. pDC were scattered around perivenular infiltration areas, and small and large lymphoid aggregations in RA. The mDC/pDC ratio increased significantly, with higher grading in RA SF tissues compared to OA synovial tissues (p<0.05). IDO-immunoreactivity was detected in pDC by serial sectioning and staining of RA synovial tissues. CONCLUSIONS Our results indicate that mature mDC play a central role in the RA inflammatory process. Although there were fewer pDC than mDC, the presence of IDO-positive pDC suggests a possible tolerance mechanism in RA synovial tissues. However, it is probably modest due to the marked inflammation in RA, in which mDC are dominant.