The rate of streptococcal eradication after intramuscular administration of benzathine penicillin G in 66 children with acute group A streptococcal pharyngitis was determined and possible reasons for treatment failure explored. Bacteriologic treatment failure, defined as isolation of the same serotype at 3- or 6-weeks follow-up, occurred in eight (12%) patients. The treatment failure rate was 21% in those with immunologically significant infection, versus 8% in those without antibody rises (P greater than 0.1). All group A beta-hemolytic streptococcal (GABS) strains isolated from patients with treatment failure, both before and after benzathine penicillin G therapy, were exquisitely susceptible to penicillin G (minimum inhibitory concentration less than or equal to 0.02 microgram/mL), and none showed evidence of tolerance (minimum bactericidal concentration less than or equal to 0.04 microgram/mL). Thus, we found GABS eradication rates to exceed 10% in children given benzathine penicillin G. The failure rate did not appear to be related to enrichment of the patient population with a high proportion of asymptomatic carriers nor to the presence of penicillin-tolerant GABS.