Group A b{beta}-hemolytic Streptococcus is the inciting agent leading to the development of acute rheumatic fever, although the exact pathogenetic mechanisms remain unexplained. Not all of the serotypes of group A streptococci can cause rheumatic fever. When some strains (e.g., M type 4) were present in a very susceptible rheumatic population, no recurrences of rheumatic fever ensued. In contrast, other serotypes prevalent in the same population caused recurrence attack rates of 20{endash}–50% of those with pharyngitis.

The concept of "rheumatogenicity" is further supported by studies suggesting that those serotypes of group A streptococci that were frequently associated with skin infection, usually the higher serotypes, were frequently isolated from the upper respiratory tract but seldom caused recurrences of rheumatic fever in individuals with a previous history of rheumatic fever. Further, certain serotypes of group A streptococci (e.g., M types 1, 3, 5, 6, 18, 24) are more frequently isolated from patients with acute rheumatic fever than are other serotypes. However, because the serotype is unknown at the time of clinical diagnosis of streptococcal pharyngitis, clinicians must assume that all group A streptococci have the capacity to cause rheumatic fever, and of all episodes of streptococcal pharyngitis should be treated accordingly.