Antibody responses (as measured by radioimmunoassay), alterations in serum levels of complement, and the presence of circulating immune complexes (as measured by the fluid-phase C1Q-binding assay, the fluid-phase conglutinin assay, and the activation of C1 were evaluated in 15 children after meningitis and/or bacteremia caused by Streptococcus pneumoniae. The ages of the children ranged from two months to 16 years; the duration of follow-up ranged from 18 to 189 days (mean, 78 days). Increases in levels of homotypic antibody were found in only three (25%) of the 12 children in whom this response could be assessed, and all of these responses were transient. Eight (53%) of the 15 children had evidence of a heterotypic antibody response to S pneumoniae serotypes other than those causing their infections. The activation of C1 and C1q-binding activity were detected at the early stage of disease and were generally transient. The result of the fluid-phase conglutinin assay was positive for 14 (93%) of the 15 children later in the course of disease; this result was consistently positive throughout the follow-up period in the majority of children. Depressed concentrations of C4 were noted in nine children, depressed levels of C3 in four, and depressed levels of factor B in two.