In 2005, the rate of macrolide resistance among GAS was estimated in France to be between 16% and 31%; however, no ad hoc epidemiological study had previously attempted to refine this estimate of resistance among patients with acute tonsillitis seen in general practice, using such a large number of strains. Primary objective - To assess the resistance rate of GAS responsible for acute tonsillitis (winter 2005-2006). Method - An epidemiological investigation conducted using a sample of general practitioners recruited from all 22 French regions. Patients aged 3 to 45 years presenting with acute tonsillitis and a positive rapid diagnostic test. Cultures, minimum inhibitory concentrations on the one hand, and molecular characterization of resistance on the other, were centralized. Results - 302 physicians included 1,180 patients. 1,149 samples were evaluable, of which 1,031 (90%) had isolated GAS. The resistance rate (I+R/CA-SFM) to erythromycin was 12.0%, 95% CI [10.1–14.2]. Resistance by age group was 14.3%, 95% CI [9.1–21.0], among 3- to 5-year-olds, 8.4%, 95% CI [5.6–12.0] among 6- to 15-year-olds, and 13.4%, 95% CI [10.7–16.5] among 16- to 45-year-olds (p=0.05). The majority of resistant strains harbored the erm(B) gene (76%) and expressed a constitutive MLSB phenotype. The remaining strains harbored the mef(A) gene (18%) and the erm(A) gene (6%). Conclusion - The current rate of SGA resistance to macrolides in France in acute tonsillitis is 12.0%, 95% CI [10.1–14.2], significantly lower than the lower limit of the 2005 estimates. (R.A.)