The susceptibility of 180 clinical isolates of Streptococcus pyrogenes from six regions of The Netherlands to the macrolide antibiotics azithromycin, clarithromycin, erythromycin and roxithromycin was analysed. The results of a microbroth MIC method, the E-test method and a disk diffusion assay were compared, and the MBC determined. In addition, the susceptibility to erythromycin of 436 clinical isolates of S. pyogenes from the Leiden region was determined. The microbroth MIC90s of azithromycin, clarithromycin, erythromycin and roxithromycin for group A streptococci were < or = 0.5 mg/L. Erythromycin had the lowest MIC90 (0.09 mg/L). The MIC data obtained with the E-test method suggested that clarithromycin and erythromycin had slightly higher anti-streptococcal activity than azithromycin and roxithromycin in vitro. MICs obtained with the E-test were lower than those found with the microbroth method. Only minor discrepancies were observed among the three methods. The MBC50 for both clarithromycin and erythromycin was 0.75 mg/L and 5.0 mg/L for azithromycin and roxithromycin. None of the 180 strains and two of the collection of 436 strains (0.5%) were resistant to erythromycin and the other macrolides tested; MICs ranged from 1 to 16 mg/L. The erythromycin-resistant strains showed an inducible type of macrolide-lincosamide-streptogramin B (MLS) resistance.