Synovial tissue from patients with rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and having menisectomies was examined by immunofluorescence for deposits of alpha-2-macroglobulin (alpha 2M). In inflammed tissues, alpha 2M was found in the synovial lining cells and in perivascular cells. The amount of alpha 2M correlated with the degree of inflammation. Similarly, free lining cells obtained by trypsination of the intact synovial membrane contained identical inclusions. alpha 2M was not detected in the menisectomy cases and in the less inflammatory osteoarthritic specimens. In-vitro studies demonstrated uptake of alpha 2M-trypsin complexes but not of native alpha 2M by most of the cultured synovial cells whether they came from rheumatoid patients or controls. The internalised complexes disappeared within 12 hours of culture. The results suggest that alpha 2M-proteinase complexes formed in the joint are taken up by phagocytic and perivascular cells in a similar way to immune complexes.