To elucidate the mechanism of cell binding to cartilage, using an immunoperoxidase technique with monoclonal antibodies against adhesion molecules, the pattern of distribution of these molecules at the rheumatoid pannus-cartilage junction has been investigated. Treatment with purified anti-human-monoclonal antibody CD54 anti-(ICAM-1) resulted in membrane staining of most of the large cells infiltrating the synovial tissue and bordering the pannus cartilage junction. When the specimen was treated with purified anti-human-monoclonal antibody CDw49d anti-(VLA-4), purified anti-human-monoclonal antibody CDw49e anti-(VLA-5), most of the cells in the cartilage pannus junction stained, but there were few staining cells against purified anti-human-monoclonal antibody CD11a anti-(LFA-1). There were some anti-ICAM-1 and anti-VLA-5 staining of the chondrocytes at or close to the junction. Human umbilical vein ECBBA1 (ELAM-1) staining was only observed on the endothelial cells of postcapillary venules in the synovial tissue. These results show that the specific adhesion molecules tested may play a role in rheumatoid pannus formation and that the increased expression of VLA-4, VLA-5, and ICAM-1 at the cartilage pannus junction may represent interaction with matrix protein. The VLA interaction appear to be involved in pannus attachment, whereas LFA-1 and ICAM-1 are involved in cell-cell interaction and may upregulate molecules such as VLA that are involved in attachment.