THERE is a considerable body of experimental evidence that the therapeutic action of penicillin rests in large part on its direct bactericidal action, and that the factor that primarily determines its therapeutic efficacy is the total time for which the drug remains at effective levels at the focus of infection.^{1 2 3 4} Thus, the number of streptococci or pneumococci surviving in an intramuscular focus in mice after an injection of aqueous sodium penicillin G was found to decrease rapidly only so long as the penicillin remained at effective levels.^{3 , 4} Extremely large doses, providing concentrations greatly in excess of the effective level, were . . .