Penicillin V, benzathine/procaine penicillin G, cefadroxil monohydrate, and erythromycin estolate were randomly assigned for therapy of group A streptococcal pharyngitis in 198 children. All patients improved with in 24 hours of initiating therapy. Reinfection with a new group A streptococcal serotype occurred in 13 patients, 12 developing 7 to 12 days after stopping therapy and 11 becoming symptomatic. Relapse with the same organism occurred in 16 patients, only 5 (31%) of whom were symptomatic. Antibody titer rises, antibiotic resistance of group A organisms, presence of penicillinase-producing staphylococci, and lack of compliance were not related to recurrent infections. There were no significant differences between the failure rates of the four test drugs: penicillin V, 12%; benzathine/procaine penicillin G, 12%; cefadroxil monohydrate, 5%; and erythromycin, 2%.