The frequency of symptomatic relapses following various antibiotic treatments for group A beta-hemolytic streptococcal tonsillopharyngitis was evaluated in 1080 pediatric patients. Within 5 days of completing therapy, the rank-order frequency of treatment failures was (1) penicillin, (2) amoxicillin, (3) first-generation cephalosporins, (4) beta-lactamase stable cephalosporins and amoxicillin-clavulanate (P = .005). Retreatment of symptomatic failures resulted in another symptomatic relapse more often with penicillin than with cephalosporins (P = .02). Clinicians should be aware that the rate of symptomatic failures after antibiotic therapy for group A beta-hemolytic streptococcal tonsillopharyngitis differs by drug and is not an uncommon event.