Hydroxyapatite crystals in spheroid-shaped masses 1.9–15.6m̈ in diameter were found in 12 of 13 synovial fluids obtained from the shoulder joints of 4 patients with rotator cuff tears and glenohumeral osteo-arthritis. Two of 16 control joint fluids also showed these particles. Collagen types I, II, and III were identified in the joint fluid pellets from 3 of the 4 patients, and fibers with typical collagen periodicity were also seen on transmission electronmicroscopy. Collagenase and neutral protease activities were found in fluids from 5 joints in 3 patients, whereas active collagenase was found in only 1 of 10 fluids from rheumatoid arthritis patients and in none of 3 fluids from patients with osteoarthritis. Neutral protease activities were present in several rheumatoid joint fluids. These findings are compatible with the hypothesis of an enzymatic release of hydroxyapatite crystals from the synovium and endocytosis by synovial macrophage-like cells with subsequent crystal-stimulated release of collagenase and neutral protease into the joint fluid, completing a pathogenetic cycle.