ABSTRACTInStreptococcus pyogenes, efflux-mediated erythromycin resistance is associated with themefgene, represented mostly bymef(A), although a small portion of strains carry differentmefsubclasses. We characterized the composite genetic elements, includingmefsubclasses other thanmef(A), associated with other resistance genes inS. pyogenesisolates. Determination of the genetic elements was performed by PCR mapping. The strains carrying mosaicmef(A/E), in which the 5′ region was identical tomef(A) and the 3′ region was identical tomef(E), also carriedtet(O). The two genes were found enclosed in an element similar toS. pyogenesprophage Φm46.1, designated the Φm46.1-like element. InS. pyogenesstrains carryingmef(E) andtet(M),mef(E) was included in a typical mega element, and in some strains, it was physically associated withtet(M) in the composite element Tn2009.S. pyogenesstrains carryingmef(I) also carriedcatQ; the two genes were linked in a fragment representing a portion of the 5216IQ complex ofStreptococcus pneumoniae, designated the defective IQ element. In the only isolate carrying a novelmefgene, this was associated withcatQandtet(M) in a genetic element similar to the 5216IQ complex ofS. pneumoniae(5216IQ-like complex), suggesting that the novelmefis in fact a variant ofmef(I). This study demonstrates that the composite elements containingmefare shared betweenS. pyogenesandS. pneumoniaeand suggests that it is important to distinguish themefsubclass on the basis of the genetic element containing it.