Serum pneumococcal antibody and opsonic activity were measured in normal and splenectomized children before and after vaccination with capsular polysaccharides of Streptococcus pneumoniae. Splenectomized children showed a lower mean antibody response to four capsular polysaccharide types after vaccination but had higher antibody levels than normal children before vaccination for 10 of the 12 antigen types. Two splenectomized children showed high serum antibody levels before vaccination but low autologous pneumococcal opsonic activity, measured with a phagocytic test that employed normal human leukocytes. Thirteen (42%) of 31 splenectomized patients and three (25%) of 12 normal subjects with a twofold pneumococcal antibody increase after vaccination failed to show an autologous opsonic response. Alternative-pathway opsonic activity was moderately reduced in five splenectomized patients; however, immunochemical measurements of C1q, C3, properdin, and factor B were normal in all patient sera. These observations suggest that vaccination with pneumococcal polysaccharides may not enhance serum opsonic activity against vaccine pneumococcal types in some splenectomized, as well as unsplenectomized, children.