We examined the expression of stromelysin mRNA (SL mRNA) in synovial biopsy specimens from 12 cases of rheumatoid arthritis (RA) and 2 cases of osteoarthritis (OA) using in situ hybridization. The study demonstrated that positive cells with high levels of SL mRNA were mostly (85%) found in the synovial lining layer. The positive cells were abundant in the synovium of RA which presented well developed lymphoid follicles with massive inflammatory cells. On the other hand, the synovium of OA contained no positive cells for SL mRNA. In addition, low yet positive levels of SL mRNA were detected in the endothelial cells and vascular myocytes, and interstitial cells in the deeper layer of the synovium. Karyometric studies showed that cells positive for SL mRNA had significantly larger and more spherical nuclei than weakly positive or negative cells. The SL mRNA positive cells did not demonstrate any immunoreactivity to markers of bone marrow origin, such as Leu M1, Leukocyte Common Antigen (LCA) and lysozyme antigen. Electron microscopy of a case with many SL mRNA positive cells showed that most had well developed rough endoplasmic reticulum and numerous processes on the cell surface, and some had also well developed rough endoplasmic reticulum but without processes indicating that they may be AB and/or B synoviocytes.