Fatal or life-threatening infection occurred in 13 members of a post-splenectomy population of 110 individuals followed for a median period of 6 years. Division of the population into two groups, one group predisposed to infection by the basic disease and/or the treatment which led to splenectomy and another non-predisposed group, revealed a distinct difference in the hazard. The non-predisposed group of 63 individuals had only one severe infection; this experience does not suggest risk of a very high order. Our Experience combined with that of others reporting cases in this category, provides a total splenectomy population of 205 with but two severe infections. It is evident that splenectomy carries a very low risk of post-operative infection when done over the age of 6 months for the generally accepted indications of splenic rupture, congenital spherocytic anemia, and idiopathic thrombocytopenic purpura. In the 47 individuals in this study predisposed to infection by their underlying disease, the incidence of severe post-operative infection was approximately 25%. No relation to age at time of splenectomy was evident. Ten of the 12 infections occurred within 12 years of operation. No attempt has been made to assess how great an increase, if any, this represents over a non-splenectomized control population similarly predisposed to infection. Our Experience, in addition to that of others, in the group predisposed to infection by their underlying disease, makes a total splenectomy population of 85; 23 (27%) of this group suffered severe post-operative infections.