Evidence has been presented to support the conclusion that epitope-specific cross-reactive autoimmunity generated in response to a microorganism can result in an inflammatory sequela. The role of this mechanism in the pathogenesis of the experimental disease, adjuvant arthritis, appears clear. In the case of human rheumatic conditions, such as rheumatic fever and the HLA-B27-associated reactive arthritides, the role is not yet established, but clinical evidence suggests that the hypothesis is an attractive one.