Rheumatic fever is a catastrophic illness in many parts of the world, particularly in developing nations, where the incidence has been estimated to be between 10 and 15 million new cases each year. In the United States, rheumatic fever had become a rarity, having virtually disappeared by the mid 1960s. Of increasing concern, however, was the abrupt rise in the incidence of rheumatic fever in the United States in the mid 1980s, with reported "outbreaks" in middle-class communities in five cities and two military camps. Recently, a number of cases of poststreptococcal reactive arthritis have been reported. On close examination, however, these are most likely alternate clinical presentations of rheumatic fever. It is widely accepted that rheumatic fever occurs following an overactive immune response by a genetically susceptible host to oropharyngeal infection with group A beta-hemolytic streptococci. Nevertheless, details of pathogenesis at a level allowing more effective intervention remain obscure. The question of pathogenesis holds a deep interest, because rheumatic fever is one of the few autoimmune diseases with a known infectious etiology.