In this study, we analyzed the antimicrobial resistance properties and T antigenic types of 511 isolates collected in Lisbon district, Portugal, from throat swabs of healthy subjects (n=341), during 2000-2002 and from diverse infection sites (n=170) of outpatients and inpatients, during 1999-2002. Erythromycin resistance was higher in tonsillitis/pharyngitis (27.4%) and skin infection isolates (21.1%), than in carriage and invasive isolates (<or=10%). Differences in erythromycin resistance among children and adults were noticed only for carriage isolates (9.3% in children and 21.1% in adults). Most erythromycin-resistant isolates from carriage (82.4%) and tonsillitis/pharyngitis (71.9%) showed the M phenotype. All M phenotype isolates (n=53) carried mef(A), whereas all MLS(B) phenotype isolates (n=19) carried erm(B) and not erm(A). Resistance to tetracycline [mediated by tet(M) in most isolates] was <or=6% in tonsillitis/pharyngitis and carriage isolates, 36.8% in skin infection isolates, and 44.1% in invasive isolates. The M phenotype increased since 2000, linked to a decrease of tetracycline resistance, and was predominantly associated with T1 in 2000-2001 and T12 in 2002 among carriage isolates, and with T8/25/Imp19 through 2000-2002 among tonsillitis/pharyngitis isolates. The majority (53%) of the tetracycline-resistant invasive isolates were nontypable. All isolates were susceptible to penicillin and chloramphenicol. This study showed that tetracycline and macrolide resistance frequency and phenotypes differ among GAS from various origins and changed over time. Moreover, T typing suggested that most drug-resistant isolates causing oropharyngeal carriage are distinct from the majority of isolates causing noninvasive and invasive infection.