Hypothesis #3 Inflammatory response causing damage to stifle joint as a result Lyme Disease. Given Bonnie's exercise history in wooded areas and that she is not, to our knowledge, currently on a tick preventitive, it is possible that she has sustained a tick-borne illness, such as Lyme Disease, which has resulted in an inflamatory response in her stifle joint. An infected tick attached to the skin and after several hours of feeding, the spirochete (Borrelia burgdorferi) was transferred to Bonnie. This resulted in a septicemia allowing the spirochete to seed the stifle joint. The spirochete causes a generalized infection of connective tissues, joint capsules, and lymph nodes. The mechanism by which the spirochete causes damage to joints is still unclear, but it is believed to be due to penetration of the joint by the spirochete itself (and the resulting antibodies produced in the joint) or to the accumulation of antibody-antigen complexes in the joint. IgG from the circulation is directed against the spirochete (antigen). This IgG binds to the spirochete forming an antigen-antibody complex which can settle in the stifle joint. Leukocytes, mainly neutrophils, and complement are directed to the joint capsule and become activated. Inflammatory mediators are then released by the synoviocytes, causing damage to surrounding tissues (cartilage and joint capsule) Pro-inflammatory mediators (cytokines, TNF-alpha, IL-1beta, prostoglandins, etc.) are released from the synoviocytes. These mediators cause the synovial lining to undergo hypertrophy and hyperplasia, and is accompanied by an increase in synovial vascular permeability. Type A synoviocytes produce an increased amount of low quality (decreased viscosity) synovial fluid. Also, the fibrous joint capsule undergoes fibroplasia and increased vascularity. The result of the hyperplasia and increased vascular permeability is joint effusion, which is consistent with our clinical history. The increase in fluid will cause pressure on the joint capsule and the nerves within the joint causing pain and resulting in lameness, which is also consistent with the history and presentation. Bonnie's clinical presentation of lameness, joint effusion, and pain in the left stifle all correlate with the gross findings of Lyme Disease. Other symptoms seen with the disease are transient and could have been overlooked by the owner. Transient lameness is common in Lyme disease and is often the first sign of the disease. Bonnie's owner brought her in relatively quickly, given a few more days the lameness may have resolved spontaneously.