Lyme disease is a newly recognized, multi-system disorder that may be associated with chronic arthritis. Of 25 patients with severe arthritic manifestations the most frequent radiographic finding was knee joint effusion. Intra-articular edema was often accompanied by a continuum of soft-tissue changes involving the infrapatellar fat pad, periarticular soft tissues, and the entheses, which were sometimes thickened, calcified, or ossified. Later in the illness, the joints of some patients showed typical changes of an inflammatory arthritis, including juxta-articular osteoporosis, cartilage loss, and cortical or marginal bone erosions. Less commonly, other patients demonstrated changes more characteristic of degenerative arthritis, including cartilage loss, subarticular sclerosis, and osteophytosis. Joint involvement of Lyme disease has similarities to juvenile arthritis and Reiter syndrome, but can usually be distinguished clinically and serologically from these entities.