Background: Emergence of erythromycin (Er) and clindamycin (C) resistance (R) observed in GBS, is currently becoming recognized. Methods: Clinical isolates were obtained from a Belgian surveillance for invasive GBS disease in newborns and adults in 1996-1998 (N1=235) and from consecutive specimens submitted, during 1999-2000, to the University hospital of Liege (N2=165). MICs of Er were determined buy using Etest® strip (interpretive criteria of NCCLS). Furthermore, for the ErR isolates, the inducible (iMLS), constitutive (cMLS) and M phenotypes were assessed by disk diffusion and by a double-disk test; the distribution of genes encoding RNA methylases and efflux pumps was investigated by PCR. Results: Of the N1 and N2 isolates, 16 (6.8%) and 19 (11.5%) were respectively R to Er. Among these 35 ErR isolates, 21 (60%) exhibited the cMLS phenotype. They demonstrated a high level R to Er with MICs ranging from 16 to >256 mg/L. The ermB gene was harbored by 19/21 isolates, the ermTR gene by 1 isolate and both ermB and ermTR were present in another isolate. The iMLS phenotype was observed in 10 (29%) ErR isolates; the ermTR gene was present in all isolates except one harboring an ermTR gene. These strains demonstrated low level of R to Er, with MICs of 1-12 mg/L. All 4 isolates (11%) expressing an M phenotype, displayed low level R to Er alone (MICs, 2 mg/L) and were positive for the mefA/B gene. Conclusion: In Belgium, by year 2000, prevalence of R to macrolide in GBS exceeded 10%. R was mainly caused by target-site modification (ermB, ermTR) mechanisms; efflux (mefA/B) R mechanism was also prevalent among the isolates tested. These results indicate the possibility of inappropriate prophylaxis or therapy using C or E as the recommended alternatives in penicillin-allergic patients.