The pattern of susceptibility to a range of antimicrobials was tested for 1485 isolates of Streptococcus pyogenes and 1547 isolates of Staphylococcus aureus included in the international PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance study (1999-2000). Overall, almost 10% of S. pyogenes isolates were erythromycin A resistant. There was a wide heterogeneity of resistance, with high levels of macrolide resistance in Poland (42%), Hong Kong (28%), Italy (25%), Portugal (24%) and Spain (21%), and no macrolide resistance in Indonesia, Austria, Belgium, the Netherlands or the UK. Using NCCLS tentative breakpoints, 97.6% of isolates were susceptible to telithromycin, with MIC90 less than or equal to 0.015 mg/L in most regions. Resistance among S. pyogenes to the beta-lactams (MIC90 less than or equal to 0.12 mg/L for all except cefaclor) and fluoroquinolones was not detected. Macrolide resistance was present among the S. aureus isolates, and as with S. pyogenes, there was a wide heterogeneity of resistance, with lower rates in Australia, Indonesia, Hungary, Austria, Germany, the Netherlands, Portugal, Sweden and Switzerland. Methicillin-resistant isolates were resistant to the beta-lactams and the macrolides. Resistance to telithromycin was detected in methicillin-resistant isolates in Latin and North America, Asia and Europe. Telithromycin resistance was non-existent or low (MIC90 range 0.06-0.25 mg/L) in Australia, Indonesia, Hungary, Austria, Germany, the Netherlands, Portugal, Sweden and Switzerland. Regardless of methicillin susceptibility, resistance to linezolid, teicoplanin or vancomycin was not apparent globally.