IN VIEW Of the success of splenectomy in dealing with certain clinical problems, and the lack of any clearly unfavorable effects of this procedure, the idea that the spleen is not physiologically essential has been widely accepted. The first serious challenge to this concept arose with the clinical observation of King and Schumaker of a high incidence of serious bacterial infection following splenectomy performed in infancy. This original report has been supplemented during the last decade by additional clinical data, and renewed interest in the role of the spleen in immunity has resulted. Recent experimental data have defined more clearly immunological functions for the spleen that are of special significance during early development. The purposes of this are paper are (1) to review the clinical problem which led to re-examination of the role of the spleen in immunity, particularly, as it relates to the early development of the immune mechanism, and (2) to offer a hypothesis which may explain the clinical observation of overwhelming infection after splenectomy in the young infant. THE CLINICAL PROBLEM In 1952 King and Schumaker reported an unusual incidence of infection in infants who had undergone splenectomy for congenital hemolytic anemia. The hazards of splenectomy in early life were pointed out in a number of papers which appeared subsequently with large series of cases reinforcing the validity of the earlier observations. Most recently Horan and Colbatch have incisively reviewed the problem and added a number of their own cases to those already in the literature. In spite of the preponderance of evidence, dissenting reports have appeared and the subject remains somewhat controversial.