Epidemiological studies have proposed an association between group A streptococci (GAS) bearing a particular M serological type and pathologic conditions such as streptococcal toxic shock syndrome (STSS). M1 and M3 GAS are isolated from STSS cases more frequently, whereas M4 and M12 GAS are isolated from non-STSS cases more frequently. To investigate whether there is any difference contributing the M-type association among GAS, we compared various virulence traits, including the murine lethality of M4, M12, M1, and M3 GAS clinical isolates, which are not clonally related to one another. Murine lethality, the activities of superantigens, streptolysin O, and nicotinamide adenine dinucleotide glycohydrolase, and the presence of the speA and speC genes were closely associated with M type. These results indicate that M types may serve, in part, as markers for strains/clones with particular profiles of virulence traits and mouse lethality.