Studies relating opsonization and IgG antibodies to Streptococcus pneumoniae have yielded contradictory results. This study compared changes in opsonization with IgG subclass response after vaccinating healthy subjects with a 23-valent pneumococcal vaccine. Total IgG and IgG subclass antibodies to pneumococcal polysaccharide types 8, 9, and 19 were measured by ELISA. Opsonic activity was assayed using 3H-labeled bacteria and polymorphonuclear leukocytes in different serum concentrations (5%-40%). A substantial postvaccination increase in total and subclass IgG antibody was observed in most subjects, although variations were seen. Postvaccination sera generally gave rise to enhanced opsonization, and a correlation was found between increases in antibody levels and opsonization. This correlation was closest for IgG1 and IgG4 and generally strongest at the lowest serum concentration, but weak or absent at the highest concentration. Thus, vaccination against S. pneumoniae stimulates a variable increase in specific opsonic activity in health persons that is best demonstrated when serum is a limiting factor in the opsonin assay.