A total of 78 clinical isolates of Streptococcus pyogenes were collected from January 1992 through December 1993 from patients in southern Taiwan. The in vitro activities of 10 antimicrobial agents were determined by the agar dilution method. Penicillin, cephalothin, cefotaxime, vancomycin, and ofloxacin were shown to be active against S. pyogenes isolates, with MICs at which 90% of isolates are inhibited (MIC90s) being < or = 0.03, < or = 0.13, < or = 0.13, < or = 0.13, and < or = 0.25 microgram/ml, respectively. Erythromycin and azithromycin both had poor activities (MIC50s, 16 and >128 micrograms/ml, respectively; MIC90s, >128 and >128 micrograms/ml, respectively). The activities of tetracycline, clindamycin, and chloramphenicol against a significant number of these isolates were also limited. As the MICs of clindamycin and chloramphenicol for the isolates increased, the MICs of the two macrolides also increased. Clindamycin, chloramphenicol, and the two macrolides were less potent against isolates recovered form throat swab samples than against those from blood or other sources. Isolates of the T12 and T1 serotypes accounted for 53.8% of all isolates. The majority (87.5%) of the isolates recovered from throat swab samples were of the T12 serotype, whereas 19.2% of the isolates recovered from blood were of the T12 serotype. In contrast, 66.7% of the isolates of the T1 serotype were derived from blood but none were derived from throat swab samples. Of the 33 T12 serotype isolates, erythromycin MICs for 78.8% of the isolates were >128 micrograms/ml. Because of the poor activities of erythromycin and azithromycin against S. pyogenes isolates from patients in southern Taiwan, these drugs should no longer be considered the drugs of choice for the management of group A streptococcal infections among patients who live in this area.