This report describes a study of hemolytic streptococcal infection during the first eight years of life. Serial study of a group of babies from birth through the fourth year demonstrated that infection by the hemolytic streptococcus was a frequent event but that the disease was usually mild or inapparent. Hemolytic streptococcal infection during the first four years of life in its more severe form was characterized by the lack of an acute onset, by low grade or absent fever, by rhinorrhea, by a protracted un-self limited course, and by the occurrence of frequent suppurative complications. Accurate etiologic diagnosis in these cases required bacteriologic study of the nasopharyngeal flora and of the purulent discharges. The administration of penicillin abruptly terminated the disease process in these cases with prompt and dramatic clinical improvement. After the fourth year the disease pattern changed so that progressively more of the infections were associated with an acute febrile onset, sore throat, exudative tonsillitis and pharyngitis, and occasionally with a skin rash. Rheumatic fever and lesser manifestations of the rheumatic state occurred following streptococcal infection in children more than 4 years of age but were never observed in younger ones. Evidence is presented which supports but does not establish the validity of the hypothesis that the changing patterns of clinical response to hemolytic streptococci are the result of repeated infection by these organisms with an alteration in tissue reactivity presumably on an immunologic basis.