Background. Concern about the emergence of antibiotic-resistant strains and about morbidity and/ormortality related to rheumatic fever and rheumatic heart disease has been a continuous impetus for the development of a safe, effective vaccine against group A Streptococcus (GAS). To date, 1120 GAS M types are known, as identified by serological typing. In general, serum immunoglobulin G directed to the hypervariable NH2 terminal portion of M protein leads to complement fixation and opsonophagocytosis of the homologous streptococcal serotype by polymorphonuclear leukocytes, and the protection is type specific. The sequence variation at the N terminus ultimately affects the binding of opsonic antibodies. Because of hypervariability in these opsonic sequences from different M types, it was relevant to use epitopes derived from these multiple sequences in a "multivalent vaccine" design for evaluation of protection against these M types of GAS. Thus, any attempts to design vaccines for a given community will require information on N terminal-sequence typing and variation. Methods. In the present study, we performed molecular characterization of isolates recovered from patients in northern India-to our knowledge, for the first time-in an attempt to study the circulating M types and their N terminal sequence variability. Results. We report tremendous diversity in GAS strains recovered from symptomatic patients, with implications on the design of appropriate vaccines. Fifty-nine isolates represented 33 different sequence types. Very few novel types and no predominant clones were found. Conclusions. The high diversity of emm types encountered in a single year suggests that any M protein-based multivalent vaccine would have to be specifically tailored for this region.