Serial samples of synovial fluid aspirated from two patients with septic arthritis were assayed for proteinases and proteinase inhibitors. Active metalloproteinases but no proteinase inhibitors were present in all samples taken prior to treatment. The levels of active metalloproteinases fell with time although proenzyme forms were still present in the fluids. Both alpha 2-macroglobulin and the tissue inhibitor of metalloproteinases were found in the septic synovial fluids after treatment commenced. It is proposed that the lack of inhibitors and the presence of active proteinases capable of digesting collagen, gelatin and proteoglycan accounts for the rapid loss of cartilage found in septic arthritis.