An enzyme-linked immunosorbent assay for the detection of immunoglobulin G, M, and A antibodies against each of the 14 polysaccharide antigens contained in a contemporary pneumococcal vaccine is described. A mean total antibody fold increase above 2 from prevaccination to 4 weeks postvaccination serum samples was found for all antigens in 12 healthy adults and 6 children. Fifty-five percent of all single fold increases determined were above 2 in the adults; the value was 64% in children. Type-specific polysaccharide antibody of the immunoglobulin G class was predominant in 4 weeks postvaccination serum samples. Further studies with assays such as the one described may lead to a better understanding of the immune response to pneumococcal polysaccharides in both normal subjects and patients at increased risk of pneumococcal infection.