Rheumatoid synovial collagenase was prepared from tissue cultures from rheumatoid arthritis patients, obtained after synovectomy. Alpha 2-macroglobulin was isolated from human plasma and complexed with collagenase or trypsin. Formation of both types of complexes was proven by sodium dodecyl sulfate and rate electrophoresis. Normal rabbits were injected intraarticularly into the right knee, on days 0, 3, and 6, with either alpha 2-macroglobulin-collagenase or alpha 2-macroglobulin-trypsin complexes. Control injections of alpha 2-macroglobulin, trypsin, or rheumatoid synovial collagenase were applied to the left knee joint cavity. Groups of rabbits were killed 18 hours, 1 week, or 3 weeks after the last injection, and cellular exudation into synovial fluid and morphologic alterations of synovium were investigated. Joints injected with alpha 2-macroglobulin showed no synovitis, while joints injected with collagenase showed an experimental synovitis. Alpha 2-macroglobulin-proteinase complexes, however, induced a synovitis, which was more severe than that occurring after injection of proteinases only. In the early stages, synovium showed perivascular accumulation of inflammatory cells, infiltration with neutrophils, proliferation of synovial cells, and exudation of inflammatory cells into synovial fluid. Later stages were characterized by infiltration with mononuclear cells and fibroplasia.