The genetic diversity of group A streptococcal (GAS) isolates obtained in 1990 from Ethiopian children with various streptococcal diseases was studied by using emm gene sequence analysis. A total of 217 GAS isolates were included: 155 and 62 isolates from throat and skin, respectively. A total of 78 different emm/st types were detected among the 217 isolates. Of these, 166 (76.5%) belonged to 52 validated reference emm types, 26 (11.9%) belonged to 16 already recognized sequence types (st types) and 25 (11.5%) belonged to 10 undocumented new sequence types. Resistance to tetracycline (148 of 217) was not correlated to emm type. Isolation rate of the classical rheumatogenic and nephritogenic strains was low from cases of acute rheumatic fever (ARF) and acute glomerulonephritis (AGN), respectively. Instead, the recently discovered st types were overrepresented among isolates from patients with ARF (3 of 7) and AGN (9 of 16) (P < 0.01) compared to isolates from subjects with tonsillitis and from healthy carriers (10 of 57 and 16 of 90, respectively). In contrast to rheumatogenic strains from the temperate regions, more than half of the isolates from ARF (four of seven) carried the genetic marker for skin preference, emm pattern D, although most of them (six of seven) were isolated from throat. Of 57 tonsillitis-associated isolates, 16 (28%) belonged to emm pattern D compared to <1% in temperate regions. As in other reports emm patterns A to C were strongly associated with throat, whereas emm pattern D did not correlate to skin. This first large-scale emm typing report from Africa has demonstrated a heterogeneous GAS population and contrasting nature of GAS epidemiology in the region.Accurate identification and typing of group A hemolytic streptococci (GAS) is an essential part of epidemiological and pathogenetic studies of streptococcal diseases. A serotyping system based on antigenic variation of a surface exposed M protein and developed by Rebecca Lancefield has been in use since 1928. Although additional serotyping systems, the T and OF typing, were developed as valuable and practical substitutes, the M typing system was considered the gold standard. However, a limited supply of antisera and the high nontypeability rate among isolates, in particular those from the tropics, challenged its continued usage. In recent years, several molecular typing systems have been reported as alternatives for M typing (4,19,25). Most of the knowledge that has been accumulated concerning GAS epidemiology is based on M typing system; hence, a molecular system that correlates with this system has practical significance. The emm typing system (4, 25) which is based on sequence analysis of PCR products of the N-terminal hypervariable region of the M protein gene, concurs with M serotyping almost 1:1 (17). In addition to its simplicity, this typing system has allowed the detection of several previously unknown GAS types from different geographic regions (5,24,32,36).