The objective was to determine the frequency of early symptomatic relapses following antibiotic treatment for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis in children from Rochester, New York; Houston, Texas; Spokane, Washington; and Los Angeles, California (2004--2006). The study included 4278 patients. The proportion with a bacteriologic relapse of GABHS tonsillopharyngitis within 1 to 5 days of completing a 10-day treatment course was 8% (penicillin and bicillin), 6% (amoxicillin), 2% (first-generation cephalosporin), and 1% (second-generation and third-generation cephalosporin; P = .0001); symptomatic relapses occurred within 6 to 20 days after completion of therapy in 16%, 14%, 9%, and 7% of cases (P = .0001). Cases from New York and Washington had higher penicillin or amoxicillin failure rates than cases from Texas and California. The frequency of symptomatic relapses of GABHS tonsillopharyngitis, therefore, differs according to the antibiotic treatment selected; the trend for such relapses being penicillin or amoxicillin > cephalosporins although geographic differences may occur.