Approximately 44% of patients develop osteoarthritis (OA) following rupture of the anterior cruciate ligament (ACL) if the injury is left unrepaired. Restoring knee stability through reconstruction, while providing symptomatic relief, has not been shown to reduce the incidence of degenerative changes. In fact, recent studies have shown that 50%-60% of ACL-reconstructed patients go on to develop degenerative changes or frank osteoarthritis. In light of these data, our group suggests that the cause of post-traumatic osteoarthritis is not biomechanical but biochemical. To test this hypothesis, we measured levels of nine cytokines which are important in modulating physiological and pathophysiological metabolism of cartilage in knee joint synovial fluid following ACL rupture. Our patient population contained both acute and chronic ACL ruptures. A total of 84 samples were collected and analyzed by enzyme-linked immunosorbent assay. On the basis of the data collected, we were able to identify subgroups of patients who, on the basis of their synovial fluid cytokine profile, may be at greater or lesser risk of developing post-traumatic OA. In general, patients displayed concentrations of interleukin-1 alpha (IL-1 alpha), basic fibroblastic growth factor (bFGF), transforming growth factor-beta (TGF-beta), granulocyte/macrophage-colony stimulating factor (GM-CSF), IL-6, and IL-8 that we interpreted as being consistent with an inflammatory reaction. Of great interest is the fact that the levels of these cytokines were very similar in patients 4 weeks after injury and in chronic patients, leading us to hypothesize that a chronic smoldering inflammatory reaction persists after resolution of the acute effusion.(ABSTRACT TRUNCATED AT 250 WORDS)