The present animal experiments revealed that repeated intra-articular administration of alpha 2-macroglobulin . trypsin complexes caused a rheumatoid-like synovitis in not preimmunized rabbits. In early stages of synovitis, acute to subacute pathomorphological alterations were observed. In later stages, the chronic infiltration was accomplished by early onset of fibroplasia in some experimental joints. Similar lesions were caused by administration of methylamine-treated alpha 2-macroglobulin, an inactive alpha 2-macroglobulin (alpha 2-M), very like that produced in the trapping of a proteinase. In contrast, administration of native plasma alpha 2-M was ineffective, whereas active trypsin produced moderate inflammation. It is felt that the present experimental model resembles immunopathological processes in human arthritides, where the occurrence of alpha 2-M . proteinase complexes was verified.