Optimum therapy of streptococcal pharyngitis is still a matter of great debate. Kill kinetics of streptococci group A were investigated under the influence of fluctuating concentrations of penicillin V, ampicillin, cefalexin and erythromycin. Antibiotic concentrations in our in vitro model were adjusted to concentrations found in vivo in tonsillar tissue, penicillin V showed superior antimicrobial activity to ampicillin, cefalexin and erythromycin. Only the eight hourly administration of concentrations determined after the in vivo administration of either 100,000 IU/kg BW penicillin or 100 mg/kg BW of ampicillin or cefalexin effectively eradicated streptococci in the kinetic model. beta-lactamase forming bacteroides did not interfere with the elimination of streptococci by non beta-lactamase stable antibiotics. These data suggest that penicillin V constitutes the optimum choice of antibiotic. Efficient eradication can be achieved by the administration of a total daily dosage of 100,000 IU/kg BW at 8 hourly intervals.