Lysozyme activity was determined in 235 sera, 258 synovial fluids, and 91 urines of patients with various articular diseases. In the serum, increased activity of the enzyme was observed in 34% of patients with rheumatoid arthritis and in a proportion of patients with gout. In general, serum lysozyme was normal in osteoarthritis and other articular diseases. Increased lysozyme activity was demonstrated in 74% of synovial fluids from rheumatoid joints. In approximately half of the estimations, the level exceeded 20 μg/ml. An increase in synovial lysozyme activity was also found in several patients with ankylosing spondylitis, acute synovitis, and gout. All patients with osteoarthritis (with one exception), tears of the semilunar cartilage, and non-sanguineous traumatic effusions had normal levels of lysozyme in the synovial fluid. In rheumatoid arthritis, synovial fluid lysozyme exceeded that in the serum in 84% of simultaneous estimations. Conversely, in osteoarthritis, the serum level of lysozyme usually exceeded that found in synovial fluid. In other forms of arthritis, the results were variable. Urinary lysozyme was always normal provided that renal function was normal. As in healthy individuals, no correlation was observed between the serum activity of lysozyme and the number of polymorphonuclears and monocytes in the venous blood of patients with various forms of arthritis. In synovial fluids, the results were more variable and were scattered over a wide range. No significant correlation was found between serum lysozyme and synovial fluid lysozyme, or between either of these values and the number of polymorphonuclears and monocytes in the corresponding fluids. Similarly, there was no correlation between the activity of lysozyme and the level of immunoglobulins (except for IgA), or the titre of the latex fixation test. Serum activity of lysozyme did not correlate with the functional class of rheumatoid arthritis. However, synovial fluid lysozyme was higher in patients who were more disabled. In simultaneously aspirated samples of synovial fluid, the level of lysozyme was higher in the more severely involved joints, and appeared to correlate best with the activity of the disease in a particular joint. As in the case of other enzymes present in synovial tissue and synovial fluids, the precise role of lysozyme in contributing to damage inflicted on intraarticular structures in the rheumatic diseases still remains to be determined.